Gene expression profile algorithm and test for likelihood of recurrence of colorectal cancer and response to chemotherapy

- Genomic Health, Inc.

Algorithm-based molecular assays that involve measurement of expression levels of prognostic and/or predictive genes, or co-expressed genes thereof, from a biological sample obtained from a cancer patient, and analysis of the measured expression levels to provide information concerning the likelihood of recurrence of colorectal cancer and/or the likelihood of a beneficial response to chemotherapy for the patient are provided herein. Methods of analysis of gene expression values of prognostic and/or predictive genes, as well as methods of identifying gene expression-tumor region ratios, tumor-associated stromal surface area, and gene cliques, i.e. genes that co-express with a validated biomarker and thus may be substituted for that biomarker in an assay, are also provided.

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Description
CROSS-REFERENCE TO RELATED APPLICATION

This application claims priority benefit of U.S. Provisional Application Ser. No. 61/174,890 filed on May 1, 2009 and U.S. Provisional Application Ser. No. 61/239,420 filed Sep. 2, 2009, each of which is incorporated herein by reference in its entirety.

TECHNICAL FIELD

The present disclosure relates to molecular diagnostic assays that provide information concerning prognosis and prediction of response to chemotherapy in colorectal cancer patients. The present disclosure also provides methods of identifying genes that co-express with one or more biomarker genes.

INTRODUCTION

Colorectal cancer is the third most common malignant neoplasm worldwide, and the second leading cause of cancer-related mortality in the United States and the European Union. It is estimated that there will be approximately 150,000 new cases diagnosed each year in the United States, with about 65% of these being diagnosed as stage II/III colorectal cancer, as discussed below.

Clinical diagnosis of colorectal cancer generally involves evaluating the progression status of the cancer using standard classification criteria. Two classification systems have been widely used in colorectal cancer, the modified Duke's (or Astler-Coller) staging systems and more recently TNM staging as developed by the American Joint Committee on Cancer. Estimates of recurrence risk and treatment decisions in colorectal cancer are currently based primarily on tumor stage.

A series of trials carried out during the 1980's demonstrated that postoperative adjuvant therapy with fluorouracil (“5-FU”) and levamisole or leucovorin (“LV”) led to a significant survival benefit for colon cancer patients. However, the benefits of adjuvant therapy are not enjoyed equally by all patients. For example, adjuvant 5-FU/LV chemotherapy has been shown to benefit a relatively small (˜3%) but statistically significant subset of patients with stage II colon cancer, while the addition of oxaliplatin significantly improved overall DFS with no survival benefit seen in with stage II disease. (See, R. Gray et al., Lancet 370:2020-29 (2007), T. Andre, et al., N Engl J Med (2004), J. Kuebler, et al, J Clin Oncol (2007).) Moreover, significant neurotoxicity and GI toxicity is common and toxic deaths (0.5% in published studies) are well documented in other randomized trials.

These results underline the importance of identifying prognostic and predictive tests which better define for individual patients their likelihood of recurrence and/or magnitude of benefit that they can expect from adjuvant chemotherapy. Under current guidelines, many patients who would be cured by surgery are unnecessarily given adjuvant therapy, while other patients who would benefit from such therapy do not receive it.

SUMMARY

Algorithm-based molecular assays that involve measurement of expression levels of prognostic and/or predictive genes, or co-expressed genes thereof, from a biological sample obtained from a cancer patient, and analysis of the measured expression levels to provide information concerning the likelihood of recurrence of colorectal cancer (Recurrence Score or RS) and/or the likelihood of a beneficial response to chemotherapy (Treatment Score or TS) for the patient are provided herein. Methods of analysis of gene expression values of prognostic and/or predictive genes, as well as methods of identifying gene cliques, i.e. genes that co-express with a validated biomarker and exhibit correlation of expression with the validated biomarker, and thus may be substituted for that biomarker in an assay, are also provided. One skilled in the art would recognize that such substitutions may impact the algorithm, for example the risk profile and weighting of the gene groups may need to be adjusted.

In exemplary embodiments, expression levels of a gene from gene subsets comprising a stromal group and a cell cycle group may be used to calculate a Recurrence Score (RS). The stromal group includes at least one of the following: BGN, FAP, INHBA, or a gene that that co-expresses with BGN, FAP, or INHBA. The cell cycle group includes at least one of the following: MYBL2, Ki-67, cMYC, MAD2L1, or a gene that co-expresses with MYBL2, Ki-67, cMYC, or MAD2L1. In other exemplary embodiments, the stromal gene is BGN and the cell cycle gene is Ki-67.

In exemplary embodiments, gene expression levels of one or more genes from additional gene subsets may be measured and used to calculate the RS, including a cell signaling group, and angiogenesis group, and/or an apoptosis group. The cell signaling group includes GADD45B and genes that co-express with GADD45B. The apoptosis group includes BIK and genes that co-express with BIK. The angiogenesis group includes EFNB2 and genes that co-express with EFNB2. The calculation may be performed on a computer programmed to execute the RS algorithm.

In exemplary embodiments, the method can further include measuring expression levels of predictive genes in a tumor sample obtained from the patient; and calculating a Treatment Score (TS) for the patient using measured gene expression levels, wherein the TS is calculated by assigning the measured expression levels to gene subsets of a TS algorithm, wherein the gene subsets comprise at least one gene each from an MSI group, an apoptosis group, and a stromal group. Calculation of the TS may be performed on a computer programmed to execute the TS algorithm. In exemplary embodiments, a benefit score for the patient based on the RS and the TS may be calculated. In exemplary embodiments, the MSI group can include AXIN2 and genes that co-express with AXIN2. In exemplary embodiments, the apoptosis group can include BIK and genes that co-express with BIK. In exemplary embodiments, the stromal group can include EFNB2 and genes that co-express with EFNB2. In exemplary embodiments, the gene subsets can further include a transcription factor group, where, e.g., the transcription factor group comprises RUNX1 and genes that co-express with RUNX1. In exemplary embodiments, the gene subsets can further include a cell cycle group, where, e.g., the cell cycle group includes MAD2L1 and HSPE1, and genes that co-express with MAD2L1 and HSPE1. In exemplary embodiments, the at least one gene from the gene subsets may be replaced by a substitute gene from the group consisting of RANBP2, BUB1, TOP2A, C20_ORF1, CENPF, STK15, AURKB, HIF1A, UBE2C, and MSH2, and genes that co-express with RANBP2, BUB1, TOP2A, C20_ORF1, CENPF, STK15, AURKB, HIF1A, UBE2C, and MSH2.

In exemplary embodiments, the expression level for each gene subset may be weighted according to a contribution of the gene subset to risk of recurrence and/or response to chemotherapy.

The present disclosure provides methods to analyze gene expression taking into account variability of expression of certain gene subsets within particular regions of the tumor. In exemplary embodiments, this method may be incorporated into a RS algorithm. For example, the gene expression levels for the stromal group may be calculated as a ratio of stromal gene expression values per stroma unit area of a colorectal tumor. Similarly, gene expression levels for the cell cycle group may be calculated as a ratio of cell cycle expression values per epithelial unit area of the colorectal tumor.

The present disclosure provides methods to estimate likelihood of colon cancer recurrence based on analysis of measurements of the surface area of the tumor-associated stroma in a colon tumor sample obtained from a patient. In exemplary embodiments, this method may be incorporated into a RS algorithm.

The present disclosure provides methods to use a threshold value for expression values used in an algorithm-based gene expression analysis, which methods involve measuring an expression level of a gene in a tissue section obtained from a patient; and comparing the measured expression level to a threshold value for said gene; wherein if the threshold value is less than the expression level of said gene, the expression value is used in an expression algorithm, and wherein if the expression level of said gene is greater than or equal to the threshold value, the expression level is used in an expression algorithm.

In exemplary embodiments, the threshold value is based on a Ct value. The threshold value can be, for example, one or more from those listed in Table 3.

The present disclosure provides gene expression analysis methods to identify a gene that is co-expressed with a target gene which methods involve normalizing microarray gene expression data for cancer tumor samples based on array probes; calculating a correlation coefficient based on gene expression levels for every unique pair of array probes; determining significant probe pairs, wherein significant probe pairs are a target gene probe and an array probe with a correlation co-efficient greater than a significant threshold value; mapping the target gene to its corresponding target gene probe, selecting a candidate probe set, wherein each candidate probe is part of a significant probe pair; and identifying a gene associated with each candidate probe; wherein said gene associated with each candidate probe is a co-expressed gene.

The present disclosure also provides methods of assessing gene expression, the method comprising measuring a normalized expression level of a gene in a cancer tumor sample obtained from a patient calculating a ratio of normalized expression of the gene to a tissue unit area in the colorectal sample, wherein the tissue unit area is a tumor-associated stroma unit area or a tumor epithelial unit area; and calculating a recurrence score (RS) or a treatment score (TS) for the patient using the ratio. In related embodiments, the gene is a stromal group gene. In related embodiments, the tissue unit area is a tumor-associated stroma unit area. In further related embodiments, the gene is a cell cycle group gene. In related embodiments, the tissue unit area is a tumor epithelial unit area unit area.

The present disclosure provides methods of determining a prognosis for a cancer patient, comprising measuring a stromal area of a tumor sample obtained from the cancer patient to obtain a Stromal Risk Score, wherein increased stromal area of the tumor sample is positively correlated with an increased risk of recurrence of cancer for said cancer patient, and generating a report based on the Stromal Risk Score. In related embodiments, the tumor sample is a colorectal cancer tumor.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a set of graphs providing hazard ratio estimates and 95% confidence intervals for gene expression from univariate Cox PH regression models of recurrence-free interval (RFI) in NSABP C-01/02 patients and CCF patients for the 65 genes that were significantly related to RFI in both studies.

FIG. 2 is a series of graphs providing hazard ratio estimates and 95% confidence intervals for gene expression from univariate Cox PH regression models of RFI in C-01/02/04/06 and CCF patients for 48 gene significantly related to RFI in both surgery only and surgery plus FU-based chemotherapy.

FIG. 3a is a graph illustrating Kaplan-Meier estimates of recurrence-free interval Stage II patients treated with surgery only, by tertile of recurrence score.

FIG. 3b is a graph illustrating Kaplan-Meier estimates of recurrence-free interval Stage III patients treated with surgery only, by tertile of recurrence score.

FIG. 4a provides a graph and a table illustrating a risk profile and recurrence scores (RS) for recurrence in Stage II colon cancer patients.

FIG. 4b provides a graph and a table illustrating a risk profile and recurrence scores (RS) for recurrence in Stage III colon cancer, surgery only patients.

FIG. 5 is a graph providing a chemotherapy benefit plot for Stage II patients.

FIG. 6 provides a collection of graphs illustrating thresholding analysis for BGN, FAP and INHBA.

FIG. 7 provides a collection of graphs illustrating thresholding analysis for cMYC, Ki-67 and MYBL2.

FIG. 8 provides a collection of graphs illustrating thresholding analysis for GADD45B.

FIG. 9 provides a collection of graphs illustrating thresholding analysis for EFNB2, RUNX1 and BIK.

FIG. 10 provides a collection of graphs illustrating thresholding analysis for MAD2L1, HSPE1 and AXIN2.

FIG. 11 is a schematic illustrating seeding of gene cliques.

FIG. 12 is a Kaplan Meier curve demonstrating group risk from the QUASAR Stage II colon cancer patients treated with surgery alone.

FIG. 13 is a risk profile plot (by Kaplan Meier curve) for risk of recurrence at five years and recurrence scores.

FIG. 14 is a graph showing stromal group score (SGS) and cell cycle group score (CCGS) in tumor-associated stroma and tumor luminal areas.

FIG. 15 is a graph showing results of analysis of stromal group score in tumor-associated stroma in six patients.

FIG. 16 is a graph showing results of analysis of variability of stromal group and cell cycle group scores, GADD45B, and RS between tumor sections taken from 11 patient blocks.

FIG. 17 is a graph showing the range of performance for multi-gene recurrence score models across all colon cancer studies

FIG. 18: Performance of two gene model including a Stromal group gene (BGN) and Cell cycle group gene (Ki-67)

FIG. 19: Performance of three gene model including a Stromal group gene (BGN), a Cell cycle group gene (Ki-67) and an Apoptosis group gene (BIK)

FIG. 20: Comparative performance of ten-gene prognostic model (RS2) vs. seven-gene prognostic model (RS) in surgery-alone patients from the QUASAR study

FIG. 21 is a variability plot for natural logarithm of stroma area for 444 colon cancer patients.

FIG. 22 is a Kaplan-Meier plot for stage II colon cancer patients stratified by stroma risk group.

FIG. 23 is a Kaplan-Meier plot for stage III colon cancer patients stratified by stroma risk group.

FIG. 24 provides Kaplan-Meier estimates for stage II colon cancer patients stratified by stroma risk group and recurrence score risk group.

FIG. 25 provides Kaplan-Meier survival curves for stage III colon cancer patients stratified by stroma risk group and recurrence score risk group.

FIG. 26 is a graph showing the effects of diluting RNA concentration on (non-normalized) gene expression (Ct) measurements of Ki-67.

DETAILED DESCRIPTION

Definitions

Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Singleton et al., Dictionary of Microbiology and Molecular Biology 2nd ed., J. Wiley & Sons (New York, N.Y. 1994), and March, Advanced Organic Chemistry Reactions, Mechanisms and Structure 4th ed., John Wiley & Sons (New York, N.Y. 1992), provide one skilled in the art with a general guide to many of the terms used in the present application.

One skilled in the art will recognize many methods and materials similar or equivalent to those described herein, which could be used in the practice of the present invention. Indeed, the present invention is in no way limited to the methods and materials described herein. For purposes of the invention, the following terms are defined below.

The terms “tumor” and “lesion” as used herein, refer to all neoplastic cell growth and proliferation, whether malignant or benign, and all pre-cancerous and cancerous cells and tissues.

The terms “cancer” and “cancerous” refer to or describe the physiological condition in mammals that is typically characterized by unregulated cell growth. Examples of cancer in the present disclosure include cancer of the gastrointestinal tract, such as invasive colorectal cancer or Dukes B (stage II) or Dukes C (stage III) colorectal cancer.

The “pathology” of cancer includes all phenomena that compromise the well-being of the patient. This includes, without limitation, abnormal or uncontrollable cell growth, metastasis, interference with the normal functioning of neighboring cells, release of cytokines or other secretory products at abnormal levels, suppression or aggravation of inflammatory or immunological response, neoplasia, premalignancy, malignancy, invasion of surrounding or distant tissues or organs, such as lymph nodes, etc.

As used herein, the terms “colon cancer” and “colorectal cancer” are used interchangeably and in the broadest sense and refer to (1) all stages and all forms of cancer arising from epithelial cells of the large intestine and/or rectum and/or (2) all stages and all forms of cancer affecting the lining of the large intestine and/or rectum. In the staging systems used for classification of colorectal cancer, the colon and rectum are treated as one organ.

According to the tumor, node, metastasis (TNM) staging system of the American Joint Committee on Cancer (AJCC) (Greene et al. (eds.), AJCC Cancer Staging Manual. 6th Ed. New York, N.Y.: Springer; 2002), the various stages of colorectal cancer are defined as follows:

Tumor: T1: tumor invades submucosal T2: tumor invades muscularis propria; T3: tumor invades through the muscularis propria into the subserose, or into the pericolic or perirectal tissues; T4: tumor directly invades other organs or structures, and/or perforates.

Node: NO: no regional lymph node metastasis; N1: metastasis in 1 to 3 regional lymph nodes; N2: metastasis in 4 or more regional lymph nodes.

Metastasis: M0: mp distant metastasis; M1: distant metastasis present.

Stage groupings: Stage I: T1 NO MO; T2 NO MO; Stage II: T3 NO MO; T4 NO MO; Stage III: any T, N1-2; MO; Stage IV: any T, any N, M1.

According to the Modified Duke Staging System, the various stages of colorectal cancer are defined as follows:

Stage A: the tumor penetrates into the mucosa of the bowel wall but not further. Stage B: tumor penetrates into and through the muscularis propria of the bowel wall; Stage C: tumor penetrates into but not through muscularis propria of the bowel wall, there is pathologic evidence of colorectal cancer in the lymph nodes; or tumor penetrates into and through the muscularis propria of the bowel wall, there is pathologic evidence of cancer in the lymph nodes; Stage D: tumor has spread beyond the confines of the lymph nodes, into other organs, such as the liver, lung or bone.

Prognostic factors are those variables related to the natural history of colorectal cancer, which influence the recurrence rates and outcome of patients once they have developed colorectal cancer. Clinical parameters that have been associated with a worse prognosis include, for example, lymph node involvement, and high grade tumors. Prognostic factors are frequently used to categorize patients into subgroups with different baseline relapse risks.

The term “prognosis” is used herein to refer to the prediction of the likelihood that a cancer patient will have a cancer-attributable death or progression, including recurrence, metastatic spread, and drug resistance, of a neoplastic disease, such as colon cancer.

The term “prognostic gene” is used herein to refer to a gene, the expression of which is correlated, positively or negatively, with a likelihood of cancer recurrence in a cancer patient treated with the standard of care. A gene may be both a prognostic and predictive gene, depending on the correlation of the gene expression level with the corresponding endpoint. For example, using a Cox proportional hazards model, if a gene is only prognostic, its hazard ratio (HR) does not change when measured in patients treated with the standard of care or in patients treated with a new intervention.

The term “prediction” is used herein to refer to the likelihood that a cancer patient will have a particular clinical response to treatment, whether positive (“beneficial response”) or negative, following surgical removal of the primary tumor. For example, treatment could include chemotherapy.

The predictive methods of the present invention can be used clinically to make treatment decisions by choosing the most appropriate treatment modalities for any particular patient. The predictive methods of the present disclosure are valuable tools in predicting if a patient is likely to respond favorably (“beneficial response”) to a treatment regimen, such as chemotherapy, surgical intervention, or both. Prediction may include prognostic factors.

The terms “predictive gene” and “response indicator gene” are used interchangeably herein to refer to a gene, the expression level of which is correlated, positively or negatively, with likelihood of beneficial response to treatment with chemotherapy. A gene may be both a prognostic and predictive gene, and vice versa, depending on the correlation of the gene expression level with the corresponding endpoint (e.g., likelihood of survival without recurrence, likelihood of beneficial response to chemotherapy). A predictive gene can be identified using a Cox proportional hazards model to study the interaction effect between gene expression levels from patients treated with treatment A compared to patients who did not receive treatment A (but may have received standard of care, e.g. treatment B). The hazard ratio (HR) for a predictive gene will change when measured in untreated/standard of care patients versus patients treated with treatment A.

As used herein, the term “expression level” as applied to a gene refers to the normalized level of a gene product, e.g. the normalized value determined for the RNA expression level of a gene or for the polypeptide expression level of a gene.

The term “gene product” or “expression product” are used herein to refer to the RNA transcription products (transcripts) of the gene, including mRNA, and the polypeptide translation products of such RNA transcripts. A gene product can be, for example, an unspliced RNA, an mRNA, a splice variant mRNA, a microRNA, a fragmented RNA, a polypeptide, a post-translationally modified polypeptide, a splice variant polypeptide, etc.

The term “RNA transcript” as used herein refers to the RNA transcription products of a gene, including, for example, mRNA, an unspliced RNA, a splice variant mRNA, a microRNA, and a fragmented RNA.

Unless indicated otherwise, each gene name used herein corresponds to the Official Symbol assigned to the gene and provided by Entrez Gene (URL: www.ncbi.nlm.nih.gov/sites/entrez) as of the filing date of this application.

The terms “correlated” and “associated” are used interchangeably herein to refer to a strength of association between two measurements (or measured entities). The disclosure provides genes and gene subsets, the expression levels of which are associated with a particular outcome measure, such as for example between the expression level of a gene and the likelihood of beneficial response to treatment with a drug or microsatellite instability (MSI) phenotype status. For example, the increased expression level of a gene may be positively correlated (positively associated) with an increased likelihood of good clinical outcome for the patient, such as an increased likelihood of long-term survival without recurrence of the cancer and/or beneficial response to a chemotherapy, and the like. Such a positive correlation may be demonstrated statistically in various ways, e.g. by a low hazard ratio. In another example, the increased expression level of a gene may be negatively correlated (negatively associated) with an increased likelihood of good clinical outcome for the patient. In that case, for example, the patient may have a decreased likelihood of long-term survival without recurrence of the cancer and/or beneficial response to a chemotherapy, and the like. Such a negative correlation indicates that the patient likely has a poor prognosis or will respond poorly to a chemotherapy, and this may be demonstrated statistically in various ways, e.g., a high hazard ratio. “Correlated” is also used herein to refer to a strength of association between the expression levels of two different genes, such that expression level of a first gene can be substituted with an expression level of a second gene in a given algorithm in view of their correlation of expression. Such “correlated expression” of two genes that are substitutable in an algorithm usually gene expression levels that are positively correlated with one another, e.g., if increased expression of a first gene is positively correlated with an outcome (e.g., increased likelihood of good clinical outcome), then the second gene that is co-expressed and exhibits correlated expression with the first gene is also positively correlated with the same outcome.

A “positive clinical outcome” and “beneficial response” can be assessed using any endpoint indicating a benefit to the patient, including, without limitation, (1) inhibition, to some extent, of tumor growth, including slowing down and complete growth arrest; (2) reduction in the number of tumor cells; (3) reduction in tumor size; (4) inhibition (i.e., reduction, slowing down or complete stopping) of tumor cell infiltration into adjacent peripheral organs and/or tissues; (5) inhibition of metastasis; (6) enhancement of anti-tumor immune response, possibly resulting in regression or rejection of the tumor; (7) relief, to some extent, of one or more symptoms associated with the tumor; (8) increase in the length of survival following treatment; and/or (9) decreased mortality at a given point of time following treatment. Positive clinical response may also be expressed in terms of various measures of clinical outcome. Positive clinical outcome can also be considered in the context of an individual's outcome relative to an outcome of a population of patients having a comparable clinical diagnosis, and can be assessed using various endpoints such as an increase in the duration of Recurrence-Free interval (RFI), an increase in the time of survival as compared to Overall Survival (OS) in a population, an increase in the time of Disease-Free Survival (DFS), an increase in the duration of Distant Recurrence-Free Interval (DRFI), and the like. An increase in the likelihood of positive clinical response corresponds to a decrease in the likelihood of cancer recurrence.

The term “risk classification” means a level of risk (or likelihood) that a subject will experience a particular clinical outcome. A subject may be classified into a risk group or classified at a level of risk based on the methods of the present disclosure, e.g. high, medium, or low risk. A “risk group” is a group of subjects or individuals with a similar level of risk for a particular clinical outcome.

The term “long-term” survival is used herein to refer to survival for a particular time period, e.g., for at least 3 years, more preferably for at least 5 years.

The term “Recurrence-Free Interval (RFI)” is used herein to refer to the time (in years) from randomization to first colon cancer recurrence or death due to recurrence of colorectal cancer.

The term “Overall Survival (OS)” is used herein to refer to the time (in years) from randomization to death from any cause.

The term “Disease-Free Survival (DFS)” is used herein to refer to the time (in years) from randomization to first colon cancer recurrence or death from any cause.

The term “Distant Recurrence-Free Interval (DRFI)” is used herein to refer to the time (in years) from surgery to the first anatomically distant cancer recurrence.

The calculation of the measures listed above in practice may vary from study to study depending on the definition of events to be either censored or not considered.

The term “tumor-associated stroma unit area” (or “sua”) is used herein to refer to a measurement of the tumor-associated stroma area surrounding a tumor. Stroma is the framework or matrix of an organ providing support to the epithelia which includes components such as blood vessels, connective tissues and lymphoid cells. In the colon, tumor-associated stroma is interposed between normal stroma, epithelia, smooth muscle and malignant epithelial cells.

The term “tumor epithelial unit area” (or “cua”) is used herein to refer to a measurement of the epithelial area of a tumor which comprises cancerous (e.g., malignant) epithelial cells. In the colon, the tumor associated epithelia cells are glandular in form, genomically clonal and are referred to as the adenocarcinoma.

The term “stromal area” as used herein, refers to the surface area of colon tumor-associated stroma in a biological sample obtained from a patient sample. The stromal area may be measured by any suitable method, such as by micrometer, or standard or digital microscopic assessment of a Hematoxylin and Eosin (H&E) section.

The term “Stromal Risk,” as used herein, refers to an estimate of recurrence risk of a patient with colon cancer based on stromal area. The amount of stromal area in a colon cancer tumor obtained from a patient is associated with the risk of recurrence of colon cancer for that patient. The greater the amount of stromal area present, the greater the risk of colon cancer recurrence. This estimate may be, for example, provided in the form of a Stromal Risk Score or Group that reflects the likelihood that a colon cancer patient will have a recurrence, such as a numeric range, descriptive categories (low, intermediate, high), etc.

The term “microarray” refers to an ordered arrangement of hybridizable array elements, e.g. oligonucleotide or polynucleotide probes, on a substrate.

The term “polynucleotide,” when used in singular or plural, generally refers to any polyribonucleotide or polydeoxyribonucleotide, which may be unmodified RNA or DNA or modified RNA or DNA. Thus, for instance, polynucleotides as defined herein include, without limitation, single- and double-stranded DNA, DNA including single- and double-stranded regions, single- and double-stranded RNA, and RNA including single- and double-stranded regions, hybrid molecules comprising DNA and RNA that may be single-stranded or, more typically, double-stranded or include single- and double-stranded regions. In addition, the term “polynucleotide” as used herein refers to triple-stranded regions comprising RNA or DNA or both RNA and DNA. The strands in such regions may be from the same molecule or from different molecules. The regions may include all of one or more of the molecules, but more typically involve only a region of some of the molecules. One of the molecules of a triple-helical region often is an oligonucleotide. The term “polynucleotide” specifically includes cDNAs. The term includes DNAs (including cDNAs) and RNAs that contain one or more modified bases. Thus, DNAs or RNAs with backbones modified for stability or for other reasons, are “polynucleotides” as that term is intended herein. Moreover, DNAs or RNAs comprising unusual bases, such as inosine, or modified bases, such as tritiated bases, are included within the term “polynucleotides” as defined herein. In general, the term “polynucleotide” embraces all chemically, enzymatically and/or metabolically modified forms of unmodified polynucleotides, as well as the chemical forms of DNA and RNA characteristic of viruses and cells, including simple and complex cells.

The term “oligonucleotide” refers to a relatively short polynucleotide, including, without limitation, single-stranded deoxyribonucleotides, single- or double-stranded ribonucleotides, RNArDNA hybrids and double-stranded DNAs. Oligonucleotides, such as single-stranded DNA probe oligonucleotides, are often synthesized by chemical methods, for example using automated oligonucleotide synthesizers that are commercially available. However, oligonucleotides can be made by a variety of other methods, including in vitro recombinant DNA-mediated techniques and by expression of DNAs in cells and organisms.

As used herein, the term “expression level” as applied to a gene refers to the level of the expression product of a gene, e.g. the normalized value determined for the RNA expression product of a gene or for the polypeptide expression level of a gene.

The term “Ct” as used herein refers to threshold cycle, the cycle number in quantitative polymerase chain reaction (qPCR) at which the fluorescence generated within a reaction well exceeds the defined threshold, i.e. the point during the reaction at which a sufficient number of amplicons have accumulated to meet the defined threshold.

The terms “threshold” or “thresholding” refer to a procedure used to account for non-linear relationships between gene expression measurements and clinical response as well as to further reduce variation in reported patient scores. When thresholding is applied, all measurements below or above a threshold are set to that threshold value. Non-linear relationship between gene expression and outcome could be examined using smoothers or cubic splines to model gene expression in Cox PH regression on recurrence free interval or logistic regression on recurrence status. Variation in reported patient scores could be examined as a function of variability in gene expression at the limit of quantitation and/or detection for a particular gene.

As used herein, the term “amplicon,” refers to pieces of DNA that have been synthesized using amplification techniquest, such as polymerase chain reactions (PCR) and ligase chain reactions.

“Stringency” of hybridization reactions is readily determinable by one of ordinary skill in the art, and generally is an empirical calculation dependent upon probe length, washing temperature, and salt concentration. In general, longer probes require higher temperatures for proper annealing, while shorter probes need lower temperatures. Hybridization generally depends on the ability of denatured DNA to re-anneal when complementary strands are present in an environment below their melting temperature. The higher the degree of desired homology between the probe and hybridizable sequence, the higher the relative temperature which can be used. As a result, it follows that higher relative temperatures would tend to make the reaction conditions more stringent, while lower temperatures less so. For additional details and explanation of stringency of hybridization reactions, see Ausubel et al., Current Protocols in Molecular Biology, Wiley Interscience Publishers, (1995).

“Stringent conditions” or “high stringency conditions”, as defined herein, typically: (1) employ low ionic strength and high temperature for washing, for example 0.015 M sodium chloride/0.0015 M sodium citrate/0.1% sodium dodecyl sulfate at 50° C.; (2) employ during hybridization a denaturing agent, such as formamide, for example, 50% (v/v) formamide with 0.1% bovine serum albumin/0.1% Ficoll/0.1% polyvinylpyrrolidone/50 mM sodium phosphate buffer at pH 6.5 with 750 mM sodium chloride, 75 mM sodium citrate at 42° C.; or (3) employ 50% formamide, 5×SSC (0.75 M NaCl, 0.075 M sodium citrate), 50 mM sodium phosphate (pH 6.8), 0.1% sodium pyrophosphate, 5×Denhardt's solution, sonicated salmon sperm DNA (50 μg/ml), 0.1% SDS, and 10% dextran sulfate at 42° C., with washes at 42° C. in 0.2×SSC (sodium chloride/sodium citrate) and 50% formamide, followed by a high-stringency wash consisting of 0.1×SSC containing EDTA at 55° C.

“Moderately stringent conditions” may be identified as described by Sambrook et al., Molecular Cloning: A Laboratory Manual, New York: Cold Spring Harbor Press, 1989, and include the use of washing solution and hybridization conditions (e.g., temperature, ionic strength and % SDS) less stringent that those described above. An example of moderately stringent conditions is overnight incubation at 37° C. in a solution comprising: 20% formamide, 5×SSC (150 mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5×Denhardt's solution, 10% dextran sulfate, and 20 mg/ml denatured sheared salmon sperm DNA, followed by washing the filters in 1×SSC at about 37-50° C. The skilled artisan will recognize how to adjust the temperature, ionic strength, etc. as necessary to accommodate factors such as probe length and the like.

The terms “splicing” and “RNA splicing” are used interchangeably and refer to RNA processing that removes introns and joins exons to produce mature mRNA with continuous coding sequence that moves into the cytoplasm of an eukaryotic cell.

As used herein, the term “exon” refers to any segment of an interrupted gene that is represented in the mature RNA product. As used herein, the term “intron” refers to any segment of DNA that is transcribed but removed from within the transcript by splicing together the exons on either side of it. “Intronic RNA” refers to mRNA derived from an intronic region of DNA. Operationally, exonic sequences occur in the mRNA sequence of a gene as defined by Ref. SEQ ID numbers. Operationally, intron sequences are the intervening sequences within the genomic DNA of a gene.

The term “co-expressed”, as used herein, refers to a statistical correlation between the expression level of one gene and the expression level of another gene. Pairwise co-expression may be calculated by various methods known in the art, e.g., by calculating Pearson correlation coefficients or Spearman correlation coefficients. Co-expressed gene cliques may also be identified using a graph theory. An analysis of co-expression may be calculated using normalized expression data.

A “computer-based system” refers to a system of hardware, software, and data storage medium used to analyze information. The minimum hardware of a patient computer-based system comprises a central processing unit (CPU), and hardware for data input, data output (e.g., display), and data storage. An ordinarily skilled artisan can readily appreciate that any currently available computer-based systems and/or components thereof are suitable for use in connection with the methods of the present disclosure. The data storage medium may comprise any manufacture comprising a recording of the present information as described above, or a memory access device that can access such a manufacture.

To “record” data, programming or other information on a computer readable medium refers to a process for storing information, using any such methods as known in the art. Any convenient data storage structure may be chosen, based on the means used to access the stored information. A variety of data processor programs and formats can be used for storage, e.g. word processing text file, database format, etc.

A “processor” or “computing means” references any hardware and/or software combination that will perform the functions required of it. For example, a suitable processor may be a programmable digital microprocessor such as available in the form of an electronic controller, mainframe, server or personal computer (desktop or portable). Where the processor is programmable, suitable programming can be communicated from a remote location to the processor, or previously saved in a computer program product (such as a portable or fixed computer readable storage medium, whether magnetic, optical or solid state device based). For example, a magnetic medium or optical disk may carry the programming, and can be read by a suitable reader communicating with each processor at its corresponding station.

As used herein, the term “surgery” applies to surgical methods undertaken for removal of cancerous tissue, including resection, laparotomy, colectomy (with or without lymphadenectomy), ablative therapy, endoscopic removal, excision, dissection, and tumor biopsy/removal. The tumor tissue or sections used for gene expression analysis may have been obtained from any of these methods.

As used herein, “graph theory” refers to a field of study in Computer Science and Mathematics in which situations are represented by a diagram containing a set of points and lines connecting some of those points. The diagram is referred to as a “graph”, and the points and lines referred to as “vertices” and “edges” of the graph. In terms of gene co-expression analysis, a gene (or its equivalent identifier, e.g. an array probe) may be represented as a node or vertex in the graph. If the measures of similarity (e.g., correlation coefficient, mutual information, alternating conditional expectation) between two genes is higher than a significant threshold, the two genes are said to be co-expressed and an edge will be drawn in the graph. When co-expressed edges for all possible gene pairs for a given study have been drawn, all maximal cliques are computed. The resulting maximal clique is defined as a gene clique. A gene clique is a computed co-expressed gene group that meets predefined criteria.

As used herein, the terms “gene clique” and “clique” refer to a subgraph of a graph in which every vertex is connected by an edge to every other vertex of the subgraph.

As used herein, a “maximal clique” is a clique in which no other vertex can be added and still be a clique.

Reference to “markers for prediction of response” with reference to 5-fluorouracil (5-FU), and like expressions, encompass within their meaning response to treatment comprising 5-FU as monotherapy, or in combination with other agents, or as prodrugs, or together with local therapies such as surgery and radiation, or as adjuvant or neoadjuvant chemotherapy, or as part of a multimodal approach to the treatment of neoplastic disease.

As used herein, the terms “5-FU-based therapy”, “5-FU based treatment”, and “5-FU therapy” are used interchangeably to refer to encompass administration of 5-FU or a prodrug thereof and further encompasses administration of 5-FU combination or 5-FU combination therapy.

“5-FU combination” or “5-FU combination therapy” refers to a combination of 5-FU and another agent. A number of agents have been combined with 5-FU to enhance the cytotoxic activity through biochemical modulation. Addition of exogenous folate in the form of 5-formyl-tetrahydrofolate (leucovorin) sustains inhibition of thymidylate synthase. Methotrexate, by inhibiting purine synthesis and increasing cellular pools of certain substrates for reactivity with 5-FU, enhances the activation of 5-FU. The combination of cisplatin and 5-FU increases the antitumor activity of 5-FU. Oxaliplatin is commonly used with 5-FU and leucovorin for treating colorectal cancer, and it may inhibit catabolism of 5-FU, perhaps by inhibiting dihydropyrimidine dehydrogenase (the enzyme that is responsible for the catabolism of 5-FU), and may also inhibit expression of thymidylate synthase. The combination of 5-FU and irinotecan, a topoisomerase-1 inhibitor, is a treatment that combines 5-FU with an agent that has a different mechanism of action. Eniluracil, which is an inactivator of dihydropyrimidine dehydrogenase, leads to another strategy for improving the efficacy of 5-FU.

“5-FU prodrug” refers to drugs that, following administration to a patient, provide for activity of 5-FU. A number of 5-FU prodrugs have been developed. For example, capecitabine (N4-pentoxycarbonyl-5′-deoxy-5-fluorcytidine) is an orally administered agent that is approved by the FDA for certain treatments including colorectal cancer. Another fluoropyrimidine that acts as a prodrug for 5-FU is florafur.

Algorithm-Based Methods and Gene Subsets

The present disclosure provides an algorithm-based molecular diagnostic assay for determining an expected clinical outcome (prognostic) and/or the likelihood that a patient with cancer will have a clinically beneficial response to chemotherapy (predictive). For example, the expression levels of the prognostic genes may be used to calculate a likelihood of colorectal cancer recurrence. The expression levels of the predictive genes, and in some cases the predictive and prognostic genes, may be used to calculate the likelihood that a patient with colorectal cancer will have a clinically beneficial response to chemotherapy. The cancer can be, for example, Stage II and/or Stage III colorectal cancer. The chemotherapy can be, for example, a 5-FU-based chemotherapy.

The present disclosure provides methods to classify a tumor based on the likelihood of cancer recurrence for a patient. The likelihood of recurrence is calculated based on expression levels of prognostic genes from particular gene subsets, wherein gene subsets include at least one gene each from a stromal group and a cell cycle group. Prognostic gene subsets may also include at least one gene from a cell signaling group, an apoptosis group, and/or a transcription factor group.

The present disclosure provides methods of classifying a tumor according to the likelihood that a patient with cancer will have a beneficial response to chemotherapy based on expression levels of predictive genes. The likelihood of a beneficial response is calculated based on expression levels of predictive genes from particular gene subsets, wherein the gene subsets include at least one gene from each of a stromal group, an apoptosis group, and a MSI group. Predictive gene subsets can also include at least one gene from a transcription factor group and/or a cell cycle group.

The gene subset identified herein as the “stromal group” includes genes that are synthesized predominantly by stromal cells and are involved in stromal response and genes that co-express with stromal group genes. “Stromal cells” are defined herein as connective tissue cells that make up the support structure of biological tissues. Stromal cells include fibroblasts, immune cells, pericytes, endothelial cells, and inflammatory cells. “Stromal response” refers to a desmoplastic response of the host tissues at the site of a primary tumor or invasion. See, e.g., E. Rubin, J. Farber, Pathology, 985-986 (2nd Ed. 1994). The stromal group includes, for example, BGN, FAP, INHBA, and genes that are co-expressed with BGN, FAP, or INHBA, wherein a gene is said to be co-expressed with a stromal gene when the expression level of the gene exhibits a Pearson correlation coefficient greater than or equal to 0.6. For example, the stromal group includes the genes and/or gene cliques shown in Tables 4, 5 and 6 (provided in specification just prior to claims). The combination of genes used from within the stromal group can vary with the method of analysis for which expression is to be evaluated. For example, the stromal group for classifying a tumor according to the likelihood of colorectal cancer recurrence includes BGN, FAP and INHBA. The gene subset herein identified as the “cell cycle group” includes genes that are involved with cell cycle functions and genes that co-express with cell cycle group genes. “Cell cycle functions” are defined herein as cell proliferation and cell cycle control, e.g. checkpoint/G1 to S phase transition. The cell cycle group thus includes genes that (1) are involved in biological pathways associated with cell cycle functions; and (2) co-express with Ki-67, cMYC, MYBL2, MAD2L1, or HSPE1, with a Pearson correlation coefficient greater than or equal to 0.4. Exemplary co-expressed genes and/or gene cliques for Ki-67, cMYC, MYBL2, MAD2L1, and HSPE1 are provided in Tables 5 and 6. The combination of genes used from within the cell cycle group can vary with the method of analysis for which expression is to be evaluated. For example, the cell cycle group for classifying a tumor according to the likelihood of colorectal cancer recurrence includes Ki-67, cMYC, MYBL2, MAD2L1, and HSPE1. The cell cycle group for classifying a tumor according to likelihood that a patient will have a beneficial response to chemotherapy includes MAD2L1 and HSPE1.

This specification discloses data demonstrating that genes associated with the stroma of a tumor are associated with an increased risk of recurrence, whereas cell cycle genes are correlated with a decreased risk of recurrence. In addition, the present disclosure provides prognostic and predictive methods that take into account the observation that expression levels for certain genes vary with respect to the regions of a tumor.

Specifically, the present disclosure provides evidence that there are higher expression levels of (1) the stromal genes in the tumor-associated stroma; and (2) the cell cycle genes in the luminal part of the tumor. The ratios of expression levels to tumor region areas vary from patient to patient. This ratio of expression between tumor-associated stroma and the luminal part of the tumor can be exploited in the prognostic and predictive methods disclosed herein.

In exemplary embodiments, expression values of stromal genes may be calculated using stromal gene expression per stroma unit area, and expression values of cell cycle genes may be calculated using cell cycle gene expression per epithelial unit area. Thus, the area of the tumor-associated stroma and the area of the tumor-luminal regions may be taken into account by the prognostic and predictive algorithms in order to increase reproducibility and accuracy of RFI prediction and prediction of response to therapy, respectively. One skilled in the art would recognize that there are many conventional methods available to capture percent stroma and percent epithelia. For example, such ratios could be obtained by examining the H&E slide immediately adjacent to the tissue sections to be analyzed. This could be performed by either a pathologist (to get a gross measurement) or by digital image analysis (to obtain a more precise measurement).

In addition, the present disclosure provides evidence that measurement of the stroma area has prognostic value to colon cancer patients. Specifically, the stromal surface area of the tumor-associate stromal region of a tumor is positively correlated with increase risk of recurrence. This risk of recurrence may be reported in the form of a Stromal Risk score, or combined with risk information obtained from other sources, such as a Recurrence Score

The gene subset herein identified as the “angiogenesis group” includes genes that regulate new blood capillary formation or that otherwise participate in “wound healing.” The angiogenesis group includes genes that (1) are involved in biological pathways associated with wound healing functions; and (2) co-express with EFNB2 with a Peason correlation coefficient greater than or equal to 0.6.

The gene subset defined herein as the “apoptosis group” includes genes which are involved in apoptosis functions and genes that co-express with apoptosis group genes. “Apoptosis functions” are defined herein as a series of cellular signaling intended to positively or negatively induce apoptosis, or programmed cell death. The apoptosis group includes BIK and genes that co-express with BIK with a Pearson correlation coefficient greater than or equal to 0.6. The gene subset defined herein as the “cell signaling group” includes genes which are involved with signaling pathways impacting cell growth and apoptosis and genes that co-express with cell signaling group genes. The cell signaling group includes GADD45B and genes that co-express with GADD45B, with a Pearson correlation coefficient greater than or equal to 0.6. Exemplary genes that co-express with GADD45B are provided in Tables 4 and 5. Table 4 provides genes for which expression is highly correlated with validated prognostic and/or predictive genes (by rank and Pearson co-expression co-efficient). Table 5 provides the results of identification of genes through gene module/clique analysis of validated gene biomarkers.

The gene subset herein defined as the “transcription factor group” includes genes which are involved with transcription factor functions and genes that co-express with transcription factor group genes. “Transcription factor functions” are defined herein as the binding of specific DNA sequences to facilitate the transcription of DNA to RNA, either alone or as part of a complex. The transcription factor group includes RUNX1 and genes that co-express with RUNX1 with a Pearson correlation coefficient greater than or equal to 0.6. Exemplary co-expressed genes and/or gene cliques encompassed by the transcription factor group are provided in Tables 5 and 6.

The gene subset defined herein as the “MSI group” includes genes which are known to have a statistically significant correlation with microsatellite instability high (MSI-H) status and genes that co-express with MSI group genes. Practice guidelines indicate that MSI-H histology is one factor to consider in making cancer screening recommendations for colorectal cancer patients. (See, e.g., NCCN Practice Guidelines in Oncology, v.2.2008.) The MSI group includes AXIN2 and genes that are (1) significantly associated with MSI-H status; or (2) co-express with AXIN2 with a correlation coefficient greater than or equal to 0.4. Exemplary co-expressed genes and/or gene cliques encompassed by the MSI group are provided in Table 5.

The present disclosure also provides methods to determine a threshold expression level for a particular gene. A threshold expression level may be calculated for a prognostic or predictive gene. A threshold expression level for a gene may be based on a normalized expression level. In one example, a Ct threshold expression level may be calculated by assessing functional forms using logistic regression.

The disclosure further provides methods to determine genes that co-express with particular target genes identified by quantitative RT-PCR (qRT-PCR), e.g. validated biomarkers relevant to a particular type of cancer. The co-expressed genes are themselves useful biomarkers. The co-expressed genes may be substituted for the prognostic or predictive gene marker with which they co-express. The methods can include identifying gene cliques from microarray data, normalizing the microarray data, computing a pairwise Spearman correlation matrix for the array probes, filtering out significant co-expressed probes across different studies, building a graph, mapping the probe to genes, and generating a gene clique report. For example, the expression levels of one or more genes of a prognostic and/or predictive gene clique may be used to calculate the likelihood that a patient with colorectal cancer will experience a recurrence and/or respond to chemotherapy. A “prognostic gene clique”, as used herein, refers to a gene clique that includes a prognostic gene. A “predictive gene clique”, as used herein, refers to a gene clique that includes a predictive gene.

Various technological approaches for determination of expression levels of the disclosed genes are set forth in this specification, including, without limitation, RT-PCR, microarrays, high-throughput sequencing, serial analysis of gene expression (SAGE) and Digital Gene Expression (DGE), which will be discussed in detail below. In particular aspects, the expression level of each gene may be determined in relation to various features of the expression products of the gene including exons, introns, protein epitopes and protein activity. One or more of the prognostic and/or predictive genes, or their expression products, may be analyzed for microsatellite instability (MSI) status.

The expression levels of prognostic and/or predictive genes may be measured in tumor tissue. For example, the tumor tissue is obtained upon surgical removal or resection of the tumor, or by tumor biopsy. The expression level of prognostic and/or predictive genes may also be measured in tumor cells recovered from sites distant from the tumor, for example circulating tumor cells, body fluid (e.g., urine, blood, blood fraction, etc.).

The expression product that is assayed can be, for example, RNA or a polypeptide. The expression product may be fragmented. For example, the assay may use primers that are complementary to target sequences of an expression product and could thus measure full transcripts as well as those fragmented expression products containing the target sequence. Further information is provided in Tables A and B (inserted in specification prior to claims).

The RNA expression product may be assayed directly or by detection of a cDNA product resulting from a PCR-based amplification method, e.g., quantitative reverse transcription polymerase chain reaction (qRT-PCR). (See e.g., U.S. Pub. No. US2006-0008809A1.) Polypeptide expression product may be assayed using immunohistochemistry (IHC). Further, both RNA and polypeptide expression products may also be is assayed using microarrays.

Clinical Utility

The algorithm-based assay and associated information provided by the practice of the methods disclosed herein facilitates physicians in making more well-informed treatment decisions, and to customize the treatment of colorectal cancer to the needs of individual patients, thereby maximizing the benefit of treatment and minimizing the exposure of patients to unnecessary treatments which may provide little or no significant benefits and often carry serious risks due to toxic side-effects.

Multi-analyte gene expression tests can be used measure the expression level of one or more genes involved in each of several relevant physiologic processes or component cellular characteristics.

The algorithm used to calculate such a score in a method disclosed herein may group the expression level values of genes. The grouping of genes may be performed at least in part based on knowledge of the contribution of the genes according to physiologic functions or component cellular characteristics, such as in the groups discussed above. The formation of groups, in addition, can facilitate the mathematical weighting of the contribution of various expression levels to the recurrence and/or treatment scores. The weighting of a gene group representing a physiological process or component cellular characteristic can reflect the contribution of that process or characteristic to the pathology of the cancer and clinical outcome. Accordingly, the present disclosure provides subsets of the prognostic and predictive genes identified herein for use in the methods disclosed herein.

Based on the determination of a recurrence and/or treatment score, patients can be partitioned into subgroups (e.g., tertiles or quartiles) based on a selected value(s) of the recurrence and/or treatment score(s), where all patients with values in a given range can be classified as belonging to a particular risk group or treatment benefit group. Thus, the values chosen will define subgroups of patients with respectively greater or lesser risk and/or greater or lesser benefit.

The utility of a gene marker in predicting colorectal cancer outcome and/or response to chemotherapy may not be unique to that marker. An alternative marker having an expression pattern that is parallel to that of a selected marker gene may be substituted for, or used in addition to, a test marker. Due to the co-expression of such genes, substitution of expression level values should have little impact on the overall prognostic and/or predictive utility of the test. The closely similar expression patterns of two genes may result from involvement of both genes in the same process and/or being under common regulatory control in colon tumor cells. The present disclosure thus contemplates the use of such co-expressed genes or gene sets as substitutes for, or in addition to, prognostic and/or predictive methods of the present disclosure.

The present methods can provide for identification of colorectal cancer patients are likely to recur after surgery, and who will benefit from adjuvant chemotherapy. Such methods can be used alone or in combination with other clinical methods for patient stratification, e.g., using pathologic (tumor grade and histology) or molecular markers (e.g., levels of expression of genes such as thymidine synthase, thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), or microsatellite instability (MSI) status).

The algorithm-based molecular assay and associated information provided by the methods disclosed herein for predicting the clinical outcome in Stage II and/or Stage III cancers of the colon and/or rectum have utility in many areas, including in the development and appropriate use of drugs to treat Stage II and/or Stage III cancers of the colon and/or rectum, to stratify cancer patients for inclusion in (or exclusion from) clinical studies, to assist patients and physicians in making treatment decisions, provide economic benefits by targeting treatment based on personalized genomic profile, and the like. For example, the recurrence score may be used on samples collected from patients in a clinical trial and the results of the test used in conjunction with patient outcomes in order to determine whether subgroups of patients are more or less likely to show a response to a new drug than the whole group or other subgroups. Further, such methods can be used to identify from clinical data subsets of patients who can benefit from therapy. Additionally, a patient is more likely to be included in a clinical trial if the results of the test indicate a higher likelihood that the patient will have a poor clinical outcome if treated with surgery alone and a patient is less likely to be included in a clinical trial if the results of the test indicate a lower likelihood that the patient will have a poor clinical outcome if treated with surgery alone.

Staging of rectal tumors can be carried out based on similar criteria as for colon tumor staging, although there are some differences resulting, for example, from differences in the arrangement of the draining lymph nodes. As a result, Stage II/III rectal tumors bear a reasonable correlation to Stage II/III colon tumors as to their state of progression. As noted above, the rate of local recurrence and other aspects of prognosis differ between rectal cancer and colon cancer, and these differences may arise from difficulties in accomplishing total resection of rectal tumors. Nevertheless, there is no compelling evidence that there is a difference between colon cancer and rectal cancer as to the molecular characteristics of the respective tumors. Tests able to predict chemotherapy treatment benefit for rectal cancer patients have utility similar in nature as described for colon cancer tests and the same markers might well have utility in both cancer types.

Tests that identify patients more likely to be those that fail to respond to standard-of-care are useful in drug development, for example in identifying patients for inclusion in clinical trials testing the efficacy of alternative drugs. For example, 30-35% of Stage III colon cancer patients fail to survive five years when treated with fluorouracil-based chemotherapy after surgical resection of tumor. Preferential inclusion of these patients in a clinical trial for a new Stage III colon cancer treatment could substantially improve the efficiency and reduce the costs of such a clinical trial.

Methods of Assaying Expression Levels of a Gene Product

The methods and compositions of the present disclosure will employ, unless otherwise indicated, conventional techniques of molecular biology (including recombinant techniques), microbiology, cell biology, and biochemistry, which are within the skill of the art. Exemplary techniques are explained fully in the literature, such as, “Molecular Cloning: A Laboratory Manual”, 2nd edition (Sambrook et al., 1989); “Oligonucleotide Synthesis” (M. J. Gait, ed., 1984); “Animal Cell Culture” (R. I. Freshney, ed., 1987); “Methods in Enzymology” (Academic Press, Inc.); “Handbook of Experimental Immunology”, 4th edition (D. M. Weir & C. C. Blackwell, eds., Blackwell Science Inc., 1987); “Gene Transfer Vectors for Mammalian Cells” (J. M. Miller & M. P. Calos, eds., 1987); “Current Protocols in Molecular Biology” (F. M. Ausubel et al., eds., 1987); and “PCR: The Polymerase Chain Reaction”, (Mullis et al., eds., 1994).

Methods of gene expression profiling include methods based on hybridization analysis of polynucleotides, methods based on sequencing of polynucleotides, and proteomics-based methods. Exemplary methods known in the art for the quantification of mRNA expression in a sample include northern blotting and in situ hybridization (Parker & Barnes, Methods in Molecular Biology 106:247-283 (1999)); RNAse protection assays (Hod, Biotechniques 13:852-854 (1992)); and PCR-based methods, such as reverse transcription PCT (RT-PCR) (Weis et al., Trends in Genetics 8:263-264 (1992)). Antibodies may be employed that can recognize sequence-specific duplexes, including DNA duplexes, RNA duplexes, and DNA-RNA hybrid duplexes or DNA-protein duplexes. Representative methods for sequencing-based gene expression analysis include Serial Analysis of Gene Expression (SAGE), and gene expression analysis by massively parallel signature sequencing (MPSS).

Reverse Transcriptase PCR (RT-PCR)

Typically, mRNA is isolated from a test sample. The starting material is typically total RNA isolated from a human tumor, usually from a primary tumor. Optionally, normal tissues from the same patient can be used as an internal control. mRNA can be extracted from a tissue sample, e.g., from a sample that is fresh, frozen (e.g. fresh frozen), or paraffin-embedded and fixed (e.g. formalin-fixed).

General methods for mRNA extraction are well known in the art and are disclosed in standard textbooks of molecular biology, including Ausubel et al., Current Protocols of Molecular Biology, John Wiley and Sons (1997). Methods for RNA extraction from paraffin embedded tissues are disclosed, for example, in Rupp and Locker, Lab Invest. 56:A67 (1987), and De Andrés et al., BioTechniques 18:42044 (1995). In particular, RNA isolation can be performed using a purification kit, buffer set and protease from commercial manufacturers, such as Qiagen, according to the manufacturer's instructions. For example, total RNA from cells in culture can be isolated using Qiagen RNeasy mini-columns. Other commercially available RNA isolation kits include MasterPure™ Complete DNA and RNA Purification Kit (EPICENTRE®, Madison, Wis.), and Paraffin Block RNA Isolation Kit (Ambion, Inc.). Total RNA from tissue samples can be isolated using RNA Stat-60 (Tel-Test). RNA prepared from tumor can be isolated, for example, by cesium chloride density gradient centrifugation.

The sample containing the RNA is then subjected to reverse transcription to produce cDNA from the RNA template, followed by exponential amplification in a PCR reaction. The two most commonly used reverse transcriptases are avilo myeloblastosis virus reverse transcriptase (AMV-RT) and Moloney murine leukemia virus reverse transcriptase (MMLV-RT). The reverse transcription step is typically primed using specific primers, random hexamers, or oligo-dT primers, depending on the circumstances and the goal of expression profiling. For example, extracted RNA can be reverse-transcribed using a GeneAmp RNA PCR kit (Perkin Elmer, Calif., USA), following the manufacturer's instructions. The derived cDNA can then be used as a template in the subsequent PCR reaction.

PCR-based methods use a thermostable DNA-dependent DNA polymerase, such as a Taq DNA polymerase. For example, TaqMan® PCR typically utilizes the 5′-nuclease activity of Taq or Tth polymerase to hydrolyze a hybridization probe bound to its target amplicon, but any enzyme with equivalent 5′ nuclease activity can be used. Two oligonucleotide primers are used to generate an amplicon typical of a PCR reaction product. A third oligonucleotide, or probe, can be designed to facilitate detection of a nucleotide sequence of the amplicon located between the hybridization sites the two PCR primers. The probe can be detectably labeled, e.g., with a reporter dye, and can further be provided with both a fluorescent dye, and a quencher fluorescent dye, as in a Taqman® probe configuration. Where a Taqman® probe is used, during the amplification reaction, the Taq DNA polymerase enzyme cleaves the probe in a template-dependent manner. The resultant probe fragments disassociate in solution, and signal from the released reporter dye is free from the quenching effect of the second fluorophore. One molecule of reporter dye is liberated for each new molecule synthesized, and detection of the unquenched reporter dye provides the basis for quantitative interpretation of the data.

TaqMan® RT-PCR can be performed using commercially available equipment, such as, for example, ABI PRISM 7700™ Sequence Detection System™ (Perkin-Elmer-Applied Biosystems, Foster City, Calif., USA), or Lightcycler (Roche Molecular Biochemicals, Mannheim, Germany). In a preferred embodiment, the 5′ nuclease procedure is run on a real-time quantitative PCR device such as the ABI PRISM 7700™ Sequence Detection System™. The system consists of a thermocycler, laser, charge-coupled device (CCD), camera and computer. The system amplifies samples in a 384-well format on a thermocycler. The RT-PCR may be performed in triplicate wells with an equivalent of 2 ng RNA input per 10 μL-reaction volume. During amplification, laser-induced fluorescent signal is collected in real-time through fiber optics cables for all wells, and detected at the CCD. The system includes software for running the instrument and for analyzing the data.

5′-Nuclease assay data are initially expressed as a threshold cycle (“Ct”). Fluorescence values are recorded during every cycle and represent the amount of product amplified to that point in the amplification reaction. The threshold cycle (Ct) is generally described as the point when the fluorescent signal is first recorded as statistically significant.

To minimize errors and the effect of sample-to-sample variation, RT-PCR is usually performed using an internal standard. The ideal internal standard gene (also referred to as a reference gene) is expressed at a constant level among cancerous and non-cancerous tissue of the same origin (i.e., a level that is not significantly different among normal and cancerous tissues), and is not significantly unaffected by the experimental treatment (i.e., does not exhibit a significant difference in expression level in the relevant tissue as a result of exposure to chemotherapy). For example, reference genes useful in the methods disclosed herein should not exhibit significantly different expression levels in cancerous colon as compared to normal colon tissue. RNAs most frequently used to normalize patterns of gene expression are mRNAs for the housekeeping genes glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) and β-actin. Exemplary reference genes used for normalization comprise one or more of the following genes: ATP5E, GPX1, PGK1, UBB, and VDAC2. Gene expression measurements can be normalized relative to the mean of one or more (e.g., 2, 3, 4, 5, or more) reference genes. Reference-normalized expression measurements can range from 0 to 15, where a one unit increase generally reflects a 2-fold increase in RNA quantity.

Real time PCR is compatible both with quantitative competitive PCR, where internal competitor for each target sequence is used for normalization, and with quantitative comparative PCR using a normalization gene contained within the sample, or a housekeeping gene for RT-PCR. For further details see, e.g. Held et al., Genome Research 6:986-994 (1996).

The steps of a representative protocol for use in the methods of the present disclosure use fixed, paraffin-embedded tissues as the RNA source. mRNA isolation, purification, primer extension and amplification can be preformed according to methods available in the art. (see, e.g., Godfrey et al. J. Molec. Diagnostics 2: 84-91 (2000); Specht et al., Am. J. Pathol. 158: 419-29 (2001)). Briefly, a representative process starts with cutting about 10 μm thick sections of paraffin-embedded tumor tissue samples. The RNA is then extracted, and protein and DNA depleted from the RNA-containing sample. After analysis of the RNA concentration, RNA is reverse transcribed using gene specific primers followed by RT-PCR to provide for cDNA amplification products.

Design of Intron-Based PCR Primers and Probes

PCR primers and probes can be designed based upon exon or intron sequences present in the mRNA transcript of the gene of interest. Primer/probe design can be performed using publicly available software, such as the DNA BLAT software developed by Kent, W. J., Genome Res. 12(4):656-64 (2002), or by the BLAST software including its variations.

Where necessary or desired, repetitive sequences of the target sequence can be masked to mitigate non-specific signals. Exemplary tools to accomplish this include the Repeat Masker program available on-line through the Baylor College of Medicine, which screens DNA sequences against a library of repetitive elements and returns a query sequence in which the repetitive elements are masked. The masked intron sequences can then be used to design primer and probe sequences using any commercially or otherwise publicly available primer/probe design packages, such as Primer Express (Applied Biosystems); MGB assay-by-design (Applied Biosystems); Primer3 (Steve Rozen and Helen J. Skaletsky (2000) Primer3 on the WWW for general users and for biologist programmers. In: Rrawetz S, Misener S (eds) Bioinformatics Methods and Protocols: Methods in Molecular Biology. Humana Press, Totowa, N.J., pp 365-386).

Other factors that can influence PCR primer design include primer length, melting temperature (Tm), and G/C content, specificity, complementary primer sequences, and 3′-end sequence. In general, optimal PCR primers are generally 17-30 bases in length, and contain about 20-80%, such as, for example, about 50-60% G+C bases, and exhibit Tm's between 50 and 80° C., e.g. about 50 to 70° C.

For further guidelines for PCR primer and probe design see, e.g. Dieffenbach, C W. et al, “General Concepts for PCR Primer Design” in: PCR Primer, A Laboratory Manual, Cold Spring Harbor Laboratory Press, New York, 1995, pp. 133-155; Innis and Gelfand, “Optimization of PCRs” in: PCR Protocols, A Guide to Methods and Applications, CRC Press, London, 1994, pp. 5-11; and Plasterer, T. N. Primerselect: Primer and probe design. Methods MoI. Biol. 70:520-527 (1997), the entire disclosures of which are hereby expressly incorporated by reference.

Tables A and B provide further information concerning the primer, probe, and amplicon sequences associated with the Examples disclosed herein.

MassARRAY® System

In MassARRAY-based methods, such as the exemplary method developed by Sequenom, Inc. (San Diego, Calif.) following the isolation of RNA and reverse transcription, the obtained cDNA is spiked with a synthetic DNA molecule (competitor), which matches the targeted cDNA region in all positions, except a single base, and serves as an internal standard. The cDNA/competitor mixture is PCR amplified and is subjected to a post-PCR shrimp alkaline phosphatase (SAP) enzyme treatment, which results in the dephosphorylation of the remaining nucleotides. After inactivation of the alkaline phosphatase, the PCR products from the competitor and cDNA are subjected to primer extension, which generates distinct mass signals for the competitor- and cDNA-derives PCR products. After purification, these products are dispensed on a chip array, which is pre-loaded with components needed for analysis with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis. The cDNA present in the reaction is then quantified by analyzing the ratios of the peak areas in the mass spectrum generated. For further details see, e.g. Ding and Cantor, Proc. Natl. Acad. Sci. USA 100:3059-3064 (2003).

Other PCR-Based Methods

Further PCR-based techniques that can find use in the methods disclosed herein include, for example, BeadArray® technology (Illumina, San Diego, Calif.; Oliphant et al., Discovery of Markers for Disease (Supplement to Biotechniques), June 2002; Ferguson et al., Analytical Chemistry 72:5618 (2000)); BeadsArray for Detection of Gene Expression® (BADGE), using the commercially available LuminexlOO LabMAP® system and multiple color-coded microspheres (Luminex Corp., Austin, Tex.) in a rapid assay for gene expression (Yang et al., Genome Res. 11:1888-1898 (2001)); and high coverage expression profiling (HiCEP) analysis (Fukumura et al., Nucl. Acids. Res. 31(16) e94 (2003).

Microarrays

Expression levels of a gene of interest can also be assessed using the microarray technique. In this method, polynucleotide sequences of interest (including cDNAs and oligonucleotides) are arrayed on a substrate. The arrayed sequences are then contacted under conditions suitable for specific hybridization with detectably labeled cDNA generated from mRNA of a test sample. As in the RT-PCR method, the source of mRNA typically is total RNA isolated from a tumor sample, and optionally from normal tissue of the same patient as an internal control or cell lines. mRNA can be extracted, for example, from frozen or archived paraffin-embedded and fixed (e.g. formalin-fixed) tissue samples.

For example, PCR amplified inserts of cDNA clones of a gene to be assayed are applied to a substrate in a dense array. Usually at least 10,000 nucleotide sequences are applied to the substrate. For example, the microarrayed genes, immobilized on the microchip at 10,000 elements each, are suitable for hybridization under stringent conditions. Fluorescently labeled cDNA probes may be generated through incorporation of fluorescent nucleotides by reverse transcription of RNA extracted from tissues of interest. Labeled cDNA probes applied to the chip hybridize with specificity to each spot of DNA on the array. After washing under stringent conditions to remove non-specifically bound probes, the chip is scanned by confocal laser microscopy or by another detection method, such as a CCD camera. Quantitation of hybridization of each arrayed element allows for assessment of corresponding mRNA abundance.

With dual color fluorescence, separately labeled cDNA probes generated from two sources of RNA are hybridized pair wise to the array. The relative abundance of the transcripts from the two sources corresponding to each specified gene is thus determined simultaneously. The miniaturized scale of the hybridization affords a convenient and rapid evaluation of the expression pattern for large numbers of genes. Such methods have been shown to have the sensitivity required to detect rare transcripts, which are expressed at a few copies per cell, and to reproducibly detect at least approximately two-fold differences in the expression levels (Schena et at, Proc. Natl. Acad. ScL USA 93(2):106-149 (1996)). Microarray analysis can be performed by commercially available equipment, following manufacturer's protocols, such as by using the Affymetrix GenChip® technology, or Incyte's microarray technology.

Serial Analysis of Gene Expression (SAGE)

Serial analysis of gene expression (SAGE) is a method that allows the simultaneous and quantitative analysis of a large number of gene transcripts, without the need of providing an individual hybridization probe for each transcript. First, a short sequence tag (about 10-14 bp) is generated that contains sufficient information to uniquely identify a transcript, provided that the tag is obtained from a unique position within each transcript. Then, many transcripts are linked together to form long serial molecules, that can be sequenced, revealing the identity of the multiple tags simultaneously. The expression pattern of any population of transcripts can be quantitatively evaluated by determining the abundance of individual tags, and identifying the gene corresponding to each tag. For more details see, e.g. Velculescu et al., Science 270:484-487 (1995); and Velculescu et al., Cell 88:243-51 (1997).

Gene Expression Analysis by Nucleic Acid Sequencing

Nucleic acid sequencing technologies are suitable methods for analysis of gene expression. The principle underlying these methods is that the number of times a cDNA sequence is detected in a sample is directly related to the relative expression of the mRNA corresponding to that sequence. These methods are sometimes referred to by the term Digital Gene Expression (DGE) to reflect the discrete numeric property of the resulting data. Early methods applying this principle were Serial Analysis of Gene Expression (SAGE) and Massively Parallel Signature Sequencing (MPSS). See, e.g., S. Brenner, et al., Nature Biotechnology 18(6):630-634 (2000). More recently, the advent of “next-generation” sequencing technologies has made DGE simpler, higher throughput, and more affordable. As a result, more laboratories are able to utilize DGE to screen the expression of more genes in more individual patient samples than previously possible. See, e.g., J. Marioni, Genome Research 18(9):1509-1517 (2008); R. Morin, Genome Research 18(4):610-621 (2008); A. Mortazavi, Nature Methods 5(7):621-628 (2008); N. Cloonan, Nature Methods 5(7):613-619 (2008).

Isolating RNA from Body Fluids

Methods of isolating RNA for expression analysis from blood, plasma and serum (See for example, Tsui N B et al. (2002) 48, 1647-53 and references cited therein) and from urine (See for example, Boom R et al. (1990) J Clin Microbiol. 28, 495-503 and reference cited therein) have been described.

Immunohistochemistry

Immunohistochemistry methods are also suitable for detecting the expression levels of genes and applied to the method disclosed herein. Antibodies (e.g., monoclonal antibodies) that specifically bind a gene product of a gene of interest can be used in such methods. The antibodies can be detected by direct labeling of the antibodies themselves, for example, with radioactive labels, fluorescent labels, hapten’ labels such as, biotin, or an enzyme such as horse radish peroxidase or alkaline phosphatase. Alternatively, unlabeled primary antibody can be used in conjunction with a labeled secondary antibody specific for the primary antibody Immunohistochemistry protocols and kits are well known in the art and are commercially available.

Proteomics

The term “proteome” is defined as the totality of the proteins present in a sample (e.g. tissue, organism, or cell culture) at a certain point of time. Proteomics includes, among other things, study of the global changes of protein expression in a sample (also referred to as “expression proteomics”). Proteomics typically includes the following steps: (1) separation of individual proteins in a sample by 2-D gel electrophoresis (2-D PAGE); (2) identification of the individual proteins recovered from the gel, e.g. my mass spectrometry or N-terminal sequencing, and (3) analysis of the data using bioinformatics.

General Description of the mRNA Isolation, Purification and Amplification

The steps of a representative protocol for profiling gene expression using fixed, paraffin-embedded tissues as the RNA source, including mRNA isolation, purification, primer extension and amplification are provided in various published journal articles. (See, e.g., T. E. Godfrey et al., J. Molec. Diagnostics 2: 84-91 (2000); K. Specht et al., Am. J. Pathol. 158: 419-29 (2001), M. Cronin, et al., Am J Pathol 164:35-42 (2004)). Briefly, a representative process starts with cutting a tissue sample section (e.g. about 10 μm thick sections of a paraffin-embedded tumor tissue sample). The RNA is then extracted, and protein and DNA are removed. After analysis of the RNA concentration, RNA repair is performed if desired. The sample can then be subjected to analysis, e.g., by reverse transcribed using gene specific promoters followed by RT-PCR.

Statistical Analysis of Gene Expression Levels in Identification of Marker Genes for Use in Prognostic and/or Predictive Methods

One skilled in the art will recognize that there are many statistical methods that may be used to determine whether there is a significant relationship between an outcome of interest (e.g., likelihood of survival, likelihood of response to chemotherapy) and expression levels of a marker gene as described here. This relationship can be presented as a continuous recurrence score (RS), or patients may stratified into risk groups (e.g., low, intermediate, high). For example, a Cox proportional hazards regression model may fit to a particular clinical endpoint (e.g., RFI, DFS, OS). One assumption of the Cox proportional hazards regression model is the proportional hazards assumption, i.e. the assumption that effect parameters multiply the underlying hazard. Assessments of model adequacy may be performed including, but not limited to, examination of the cumulative sum of martingale residuals. One skilled in the art would recognize that there are numerous statistical methods that may be used (e.g., Royston and Parmer (2002), smoothing spline, etc.) to fit a flexible parametric model using the hazard scale and the Weibull distribution with natural spline smoothing of the log cumulative hazards function, with effects for treatment (chemotherapy or observation) and RS allowed to be time-dependent. (See, P. Royston, M. Parmer, Statistics in Medicine 21(15:2175-2197 (2002).) The relationship between recurrence risk and (1) recurrence risk groups; and (2) clinical/pathologic covariates (e.g., number of nodes examined, pathological T stage, tumor grade, MSI status, lymphatic or vascular invasion, etc.) may also be tested for significance.

Many statistical methods may be used to determine if there is a significant interaction between expression levels of predictive genes and beneficial response to treatment (“treatment benefit”). For example, this relationship can be presented as a continuous treatment score (TS), or patients may stratified into benefit groups (e.g., low, intermediate, high). The interaction studied may vary, e.g. standard of care vs. new treatment, or surgery alone vs. surgery followed by chemotherapy. For example, a Cox proportional hazards regression could be used to model the follow-up data, i.e. censoring time to recurrence at a certain time (e.g., 3 years) after randomization for patients who have not experienced a recurrence before that time, to determine if the TS is associated with the magnitude of chemotherapy benefit. One might use the likelihood ratio test to compare the reduced model with RS, TS and the treatment main effect, with the full model that includes RS, TS, the treatment main effect, and the interaction of treatment and TS. A pre-determined p-value cut-off (e.g., p<0.05) may be used to determine significance.

Alternatively, the method of Royston and Parmer (2002) can be used to fit a flexible parametric model using the hazard scale and the Weibull distribution with natural spline smoothing of the log cumulative hazards function, with effects for treatment (chemotherapy or observation), RS, TS and the interaction of TS with treatment, allowing the effects of RS, TS and TS interaction with treatment to be time dependent. To assess relative chemotherapy benefit across the benefit groups, pre-specified cut-points for the RS and TS may be used to define low, intermediate, and high chemotherapy benefit groups. The relationship between treatment and (1) benefit groups; and (2) clinical/pathologic covariates may also be tested for significance. For example, one skilled in the art could identify significant trends in absolute chemotherapy benefit for recurrence at 3 years across the low, intermediate, and high chemotherapy benefit groups for surgery alone or surgery followed by chemotherapy groups. An absolute benefit of at least 3-6% in the high chemotherapy benefit group would be considered clinically significant.

In an exemplary embodiment, power calculations were carried for the Cox proportional hazards model with a single non-binary covariate using the method proposed by F. Hsieh and P. Lavori, Control Clin Trials 21:552-560 (2000) as implemented in PASS 2008.

Coexpression Analysis

The present disclosure provides genes that co-express with particular prognostic and/or predictive gene that has been identified as having a significant correlation to recurrence and/or treatment benefit. To perform particular biological processes, genes often work together in a concerted way, i.e. they are co-expressed. Co-expressed gene groups identified for a disease process like cancer can serve as biomarkers for disease progression and response to treatment. Such co-expressed genes can be assayed in lieu of, or in addition to, assaying of the prognostic and/or predictive gene with which they are co-expressed.

One skilled in the art will recognize that many co-expression analysis methods now known or later developed will fall within the scope and spirit of the present invention. These methods may incorporate, for example, correlation coefficients, co-expression network analysis, clique analysis, etc., and may be based on expression data from RT-PCR, microarrays, sequencing, and other similar technologies. For example, gene expression clusters can be identified using pair-wise analysis of correlation based on Pearson or Spearman correlation coefficients. (See, e.g., Pearson K. and Lee A., Biometrika 2, 357 (1902); C. Spearman, Amer. J. Psychol 15:72-101 (1904); J. Myers, A. Well, Research Design and Statistical Analysis, p. 508 (2nd Ed., 2003).) In general, a correlation coefficient of equal to or greater than 0.3 is considered to be statistically significant in a sample size of at least 20. (See, e.g., G. Norman, D. Streiner, Biostatistics: The Bare Essentials, 137-138 (3rd Ed. 2007).)

General Description of Exemplary Embodiments

This disclosure provides a method to determine a patient's likelihood of experiencing a cancer recurrence by assaying expression levels of certain prognostic genes from a tumor sample obtained from the patient. Such methods involve use of gene subsets that are created based on similar functions of gene products. For example, prognostic methods disclosed herein involve assaying expression levels of gene subsets that include at least one gene each from each of a stromal group and a cell cycle group, and calculating a recurrence score (RS) for the patient by weighting the expression levels of each of the gene subsets by their respective contributions to cancer recurrence. The weighting may be different for each gene subset, and may be either positive or negative. For example, the stromal group score could be weighted by multiplying by a factor of 0.15, the cell cycle group score by a factor of −0.3, the cell signaling group score by a factor of 0.15, and so on. Gene subsets in such prognostic methods can further include at least one gene from a cell signaling group, apoptosis group, or transcription factor group.

For example, the weights assigned to each gene subset in the exemplary embodiments is set forth below:
RS1=Ws×Stromal Group Score+Wz×Angiogenesis Group Score−Wcc×Cell Cycle Group Score+Wcs×Cell Signaling Group Score−Wa×Apoptosis Group Score

Where:

    • Stromal Group Score=(SG1+ . . . SGn)/n (SG=Stromal gene normalized expression level (NEL))
    • Cell Cycle Group Score=(CCG1+ . . . CCGn)/n (CCG=Cell cycle gene NEL)
    • Cell Signaling Group Score=(CSG1+ . . . CSGn) (CSG=Cell signaling gene NEL)
    • Apoptosis Group Score=(AG1+ . . . AGn)/n (AG=Apoptosis gene)
    • Angiogenesis Group Score=(AgG1+ . . . AgGn)/n (AgG=Angiogenesis gene)
    • Wx=weighting factor for each gene subset

Alternatively, the genes within each gene subset may be weighted individually. Assuming standardized expression, the weights assigned to each gene subset in the exemplary embodiment is set forth below:
Stromal Group Score2=+BGN score+FAP score+INHBA score
Cell Cycle Group Score2=−2[Ki-67 score+MAD2L1 score+0.75(cMYC score)+0.25(MYBL2 score)]
Apoptosis Group Score2=−2(BIK score)
Cell Signaling Group Score2=+0.33(GADD45B score)
Angiogenesis Group Score2=+EFNB2 score

To translate the RS2 model into non-standardized expression, the weights may be divided by gene standard deviation. For example, assuming non-standardized expression, the weights assigned to each gene subset in the exemplary embodiment is set forth below:
Stromal Group Scorens=+1.06(BGN score)+1.38(FAP score)+1.14(INHBA score)
Angiogenesis Group Scorens=+1.34(EFNB2)
Cell Signaling Group Scorens=+0.44GADD45B
Cell Cycle Group Scorens=−2[1.85(Ki-67 score)+1.32(MAD2L1+0.83(cMYC score)+0.45(MYBL2 score)]
Apoptosis Group Scorens=−2(BIK score)

In exemplary embodiments, RS is calculated using expression levels of one or more of BGN, FAP, INHBA, EFNB2, MYBL2, Ki-67, cMYC, MAD2L1, HSPE1, GADD45B, BIK, and RUNX1. The disclosure provides substitute prognostic genes, the expression levels of which may similarly be used to calculate RS. These substitute predictive genes include genes that co-express with BGN, FAP, INHBA, EFNB2, MYBL2, Ki-67, cMYC, MAD2L1, HSPE1, GADD45B, BIK, or RUNX1

The RSu (recurrence score unscaled) may be rescaled, for example to be between 0 and 100. More particularly, the RSu may be rescaled as follows:

RS = { 0 if 44 × ( RS U + 0.82 ) < 0 44 × ( RS U + 0.82 ) if 0 44 × ( RS U + 0.82 ) 100 100 if 44 × ( RS U + 0.82 ) > 100

The RS may be used to determine a recurrence risk group for each patient. For example, recurrence scores may be divided into three risk classification groups using predefined cut-points. The cut-points between the low, intermediate, and high recurrence risk groups may be defined, for example, as in Table 1.

TABLE 1 Recurrence Risk Stratification Recurrence Risk Group Recurrence Score Low risk of recurrence Less than 30 Intermediate risk of Greater than or equal to 30 recurrence and less than 41 High risk of recurrence Greater than or equal to 41

The RS may be rounded to the nearest integer before the cut-points defining recurrence risk groups are applied.

The disclosure also provides methods to determine the likelihood that a patient with colorectal cancer will have a beneficial response to chemotherapy including assaying expression levels of predictive genes, where the expression levels are used in an algorithm based on gene subsets that include at least one gene each from a growth factor receptor group, an apoptosis group, and a MSI group, and calculating a treatment score (TS) for the patient by weighting the expression levels of each of the gene subsets by their respective contributions to response to chemotherapy. The weighting may be different for each gene subset, and may be either positive or negative. For example, the stromal group could be weighted by multiplying by a factor of −0.3, the transcription factor by a factor of −0.04, the apoptosis group by a factor of 0.3, the cell cycle group by a factor of 0.1, and the MSI group by a factor of 0.1. The gene subsets may additionally comprise at least one gene from a transcription factor group and/or a cell cycle group.

In the exemplary embodiments, the weights assigned to each gene subset is set forth below:
TS=−Ws×Stromal Group Score−Wtf×Transcription Factor Group Score+Wa×Apoptosis Group Score+Wcc×Cell Cycle Group Score+Wmsi×MSI Group Score

    • Where:
      • Stromal Group Score=(SG1+ . . . SGn) (SG=stromal gene normalized expression level (NEL))
      • Transcription Factor Group Score=(TFG1+ . . . TFGn) (TFG=transcription factor gene NEL)
      • Apoptosis Group Score=(AG1+ . . . AGn) (AG=apoptosis gene NEL)
      • Cell Cycle Group Score=(CCG1+ . . . CCGn) (CCG=cell cycle gene NEL)
      • MSI Group Score=(MG1+ . . . MGn) (MG=MSI gene NEL)
      • Wx=weighting factor for each gene subset

In exemplary embodiments, TS is calculated using expression levels for AXIN2, BIK, EFNB2, HSPE1, MAD2L1, and RUNX1.

The disclosure provides other predictive genes, the expression levels of which may similarly be used to calculate a TS. These substitute predictive genes include RANBP2, BUB1, TOP2A, C20_ORF1, CENPF, STK15, AURKB, HIF1A, UBE2C, and MSH2, and gene that co-express with said substitute predictive genes with a Pearson correlation co-efficient of at least 0.60.

The TSu (Treatment Score unsealed) may be rescaled, for example it may be rescaled to be between 0 and 100. More particularly, TSu may be rescaled as follows:

TS = { 0 if 37 × ( TS U - 1 ) < 0 37 × ( TS U - 1 ) if 0 37 × ( TS U - 1 ) 100 100 if 37 × ( TS U - 1 ) > 100

In addition, the TS may be used to determine a “benefit score” for each patient. For example, the patient may be classified as one who is expected to have a low, medium, or high benefit from chemotherapy. In a particular example, the RS, TS, and predefined cut-points can be used to determine a benefit score for each patient. The low, intermediate, and high benefit scores or groups may be defined as in Table 2.

TABLE 2 Beneficial Response to Chemotherapy Stratification X = 0.859exp[1.839×RSu +3.526−1.781×TSu] Benefit Group 0.859exp[1.839×RSu] Low Benefit X less than 2% Intermediate Benefit X greater than or equal to 2% and less than 6% High Benefit X greater than or equal to 6%

Data Aggregation

The expression data may be aggregated. The purpose of data aggregation is to combine information across replicate qRT-PCR wells for individual genes. For example, during qRT-PCR, triplicate wells may be run for each gene and sample. Valid triplicate wells for each gene may be aggregated into a single weighted average Ct value. The resulting weighted average Ct effectively down weights the influence of outlier observations. The data aggregation module may include the following steps for each gene and sample:

    • (1) Retrieve calculated Ct values and status data.
    • (2) Aggregate plate level statistics and record module version, date and time of processing.
    • (3) Aggregate Ct values for each gene and store statistics using all wells (valid and invalid).
    • (4) Compute gene validity based on the number of valid wells.
    • (5) Compute the weighted average of the valid wells for each gene.

Normalization of Expression Levels

The expression data used in the methods disclosed herein can be normalized. Normalization refers to a process to correct for (normalize away), for example, differences in the amount of RNA assayed and variability in the quality of the RNA used, to remove unwanted sources of systematic variation in Ct measurements, and the like. With respect to RT-PCR experiments involving archived fixed paraffin embedded tissue samples, sources of systematic variation are known to include the degree of RNA degradation relative to the age of the patient sample and the type of fixative used to store the sample. Other sources of systematic variation are attributable to laboratory processing conditions.

Assays can provide for normalization by incorporating the expression of certain normalizing genes, which genes do not significantly differ in expression levels under the relevant conditions. Exemplary normalization genes include housekeeping genes such as PGK1 and UBB. (See, e.g., E. Eisenberg, et al., Trends in Genetics 19(7):362-365 (2003).) Normalization can be based on the mean or median signal (CT) of all of the assayed genes or a large subset thereof (global normalization approach). In general, the normalizing genes, also referred to as reference genes should be genes that are known not to exhibit significantly different expression in colorectal cancer as compared to non-cancerous colorectal tissue, and are not significantly affected by various sample and process conditions, thus provide for normalizing away extraneous effects.

Unless noted otherwise, normalized expression levels for each mRNA/tested tumor/patient will be expressed as a percentage of the expression level measured in the reference set. A reference set of a sufficiently high number (e.g. 40) of tumors yields a distribution of normalized levels of each mRNA species. The level measured in a particular tumor sample to be analyzed falls at some percentile within this range, which can be determined by methods well known in the art.

In exemplary embodiments, one or more of the following genes are used as references by which the expression data is normalized: ATP5E, GPX1, PGK1, UBB, and VDAC2. The calibrated weighted average Ct measurements for each of the prognostic and predictive genes may be normalized relative to the mean of five or more reference genes.

Those skilled in the art will recognize that normalization may be achieved in numerous ways, and the techniques described above are intended only to be exemplary, not exhaustive.

Bridging Expression Measurements and Calibration

An oligonucleotide set represents a forward primer, reverse primer, and probe that are used to build a primer and probe (P3) pool and gene specific primer (GSP) pool. Systematic differences in RT-PCR cycle threshold (Ct) measurements can result between different oligonucleotide sets due to inherent variations oligonucleotide syntheses. For example, differences in oligonucleotide sets may exist between development, production (used for validation), and future production nucleotide sets. Thus, use of statistical calibration procedures to adjust for systematic differences in oligonucleotide sets resulting in translation in the gene coefficients used in calculating RS and TS may be desirable. For example, for each of the genes assayed for use in an algorithm, one may use a scatterplot of Ct measurements for production oligonucleotide sets versus Ct measurements from a corresponding sample used in different oligonucleotide set to create linear regression model that treats the effect of lot-to-lot differences as a random effect. Examination of such a plot will reveal that the variance of Ct measurements increases exponentially as a function of the mean Ct. The random effects linear regression model can be evaluated with log-linear variance, to obtain a linear calibration equation. A calculated mean squared error (MSE) for the scores can be compared to the MSE if no calibration scheme is used at all.

As another example, a latent variable measurement of Ct (e.g. first principle component) may be derived from various oligonucleotide sets. The latent variable is a reasonable measure of the “true” underlying Ct measurement. Similar to the method described above, a linear regression model may be fit to the sample pairs treating the effects of differences as a random effect, and the weighted average Ct value adjusted to a calibrated Ct.

Centering and Data Compression/Scaling

Systematic differences in the distribution of patient RS and TS due to analytical or sample differences may exist between early development, clinical validation and commercial samples. A constant centering tuning parameter may be used in the algorithm to account for such difference.

Data compression is a procedure used to reduce the variability in observed normalized Ct values beyond the limit of quantitation (LOQ) of the assay. Specifically, for each of the colon cancer assay genes, variance in Ct measurements increase exponentially as the normalized Ct for a gene extends beyond the LOQ of the assay. To reduce such variation, normalized Ct values for each gene may be compressed towards the LOQ of the assay. Additionally, normalized Ct values may be resealed. For example, normalized Ct values of the prognostic, predictive, and reference genes may be resealed to a range of 0 to 15, where a one-unit increase generally reflects a 2-fold increase in RNA quantity.

Threshold Values

The present invention describes a method to determine a threshold value for expression of a cancer-related gene, comprising measuring an expression level of a gene, or its expression product, in a tumor section obtained from a cancer patient, normalizing the expression level to obtain a normalized expression level, calculating a threshold value for the normalized expression level, and determining a score based on the likelihood of recurrence or clinically beneficial response to treatment, wherein if the normalized expression level is less than the threshold value, the threshold value is used to determine the score, and wherein if the normalized expression level is greater or equal to the threshold value, the normalized expression level is used to determine the score.

For example, a threshold value for each cancer-related gene may be determined through examination of the functional form of relationship between gene expression and outcome. Examples of such analyses are presented for Cox PH regression on recurrence free interval where gene expression is modeled using natural splines and for logistic regression on recurrence status where gene expression is modeled using lowess smoother.—(See, e.g., FIGS. 6-10.)

Thresholded Ct values for each prognostic, predictive, and reference genes can be used to calculate RS and TS. Exemplary thresholded Ct values for the 18-gene assay described herein are set forth in Table 3.

TABLE 3 Gene expression panel and threshold values Accession Accession Thres- Gene Number Threshold Gene Number hold ATP5E NM_006886 None MYBL2 NM_002466 6 GPX1 NM_000581 None Ki-67 NM_002417 6 PGK1 NM_000291 None GADD45B NM_015675 4.5 UBB NM_018955 None EFNB2 NM_004093 4 VDAC2 NM_003375 None RUNX1 NM_001754 4.5 BGN NM_001711 None BIK NM_001197 4.5 FAP NM_004460 6 MAD2L1 NM_002358 3 INHBA NM_002192 None HSPE1 NM_002157 None cMYC NM_002467 None AXIN2 NM_004655 None

Thresholded Ct values for each gene are calculated according to the formula:

{ if Normalized C T < Threshold Threshold C T = Threshold if Normalized C T Threshold Threshold C T = Normalized C T

It will be appreciated by one of ordinary skill in the art that a purpose of thresholding is to address non-linear functional forms for gene expression measurements. However, it will be readily appreciated that other nonlinear transforms other than thresholding can be used to accomplish the same effect.

Building Gene Cliques from Validated Biomarkers

This disclosure contemplates using co-expressed genes and/or gene cliques, identified with respect to prognostic and/or predictive genes, as substitutes for, or for analysis with, the prognostic and/or predictive genes disclosed herein. One method disclosed to analyze gene cliques that co-express with a target gene (i.e., a gene of interest) involves normalizing microarray gene expression data for cancer tumor samples based on array probes, calculating a correlation coefficient (e.g., using Spearman or Pearson correlation coefficients) based on gene expression levels for every unique pair of array probes, determining significant probe pairs, wherein significant probe pairs are a target gene probe and an array probe with a correlation co-efficient greater than a significant threshold value (e.g., a Spearman correlation co-efficient ≥0.5), mapping the target gene to its corresponding target gene probe, selecting a candidate probe set, wherein each candidate probe is part of a significant probe pair, and identifying an official gene symbol for each candidate probe (e.g., Entrez Gene Symbol). For example, Table 6 lists the gene cliques associated with FAP, INHBA, Ki-67, HSPE1, MAD2L1, and RUNX1.

Kits of the Invention

The materials for use in the methods of the present invention are suited for preparation of kits produced in accordance with well known procedures. The present disclosure thus provides kits comprising agents, which may include gene-specific or gene-selective probes and/or primers, for quantitating the expression of the disclosed genes for predicting prognostic outcome or response to treatment. Such kits may optionally contain reagents for the extraction of RNA from tumor samples, in particular fixed paraffin-embedded tissue samples and/or reagents for RNA amplification. In addition, the kits may optionally comprise the reagent(s) with an identifying description or label or instructions relating to their use in the methods of the present invention. The kits may comprise containers (including microliter plates suitable for use in an automated implementation of the method), each with one or more of the various reagents (typically in concentrated form) utilized in the methods, including, for example, pre-fabricated microarrays, buffers, the appropriate nucleotide triphosphates (e.g., dATP, dCTP, dGTP and dTTP; or rATP, rCTP, rGTP and UTP), reverse transcriptase, DNA polymerase, RNA polymerase, and one or more probes and primers of the present invention (e.g., appropriate length poly(T) or random primers linked to a promoter reactive with the RNA polymerase). Mathematical algorithms used to estimate or quantify prognostic or predictive information are also properly potential components of kits.

Reports

The methods of this invention, when practiced for commercial diagnostic purposes, generally produce a report or summary of information obtained from the herein-described methods. For example, a report may include information concerning expression levels of prognostic and/or predictive genes, a prediction of the predicted clinical outcome or response to chemotherapy for a particular patient, or gene cliques or thresholds. The methods and reports of this invention can further include storing the report in a database. The method can create a record in a database for the subject and populate the record with data. The report may be a paper report, an auditory report, or an electronic record. The report may be displayed and/or stored on a computing device (e.g., handheld device, desktop computer, smart device, website, etc.). It is contemplated that the report is provided to a physician and/or the patient. The receiving of the report can further include establishing a network connection to a server computer that includes the data and report and requesting the data and report from the server computer.

Computer Program

The values from the assays described above, such as expression data, recurrence score, treatment score and/or benefit score, can be calculated and stored manually. Alternatively, the above-described steps can be completely or partially performed by a computer program product. The present invention thus provides a computer program product including a computer readable storage medium having a computer program stored on it. The program can, when read by a computer, execute relevant calculations based on values obtained from analysis of one or more biological sample from an individual (e.g., gene expression levels, normalization, thresholding, and conversion of values from assays to a score and/or graphical depiction of likelihood of recurrence/response to chemotherapy, gene co-expression or clique analysis, and the like). The computer program product has stored therein a computer program for performing the calculation.

The present disclosure provides systems for executing the program described above, which system generally includes: a) a central computing environment; b) an input device, operatively connected to the computing environment, to receive patient data, wherein the patient data can include, for example, expression level or other value obtained from an assay using a biological sample from the patient, or microarray data, as described in detail above; c) an output device, connected to the computing environment, to provide information to a user (e.g., medical personnel); and d) an algorithm executed by the central computing environment (e.g., a processor), where the algorithm is executed based on the data received by the input device, and wherein the algorithm calculates a RS, TS, risk or benefit group classification, gene co-expression analysis, thresholding, or other functions described herein. The methods provided by the present invention may also be automated in whole or in part.

All aspects of the present invention may also be practiced such that a limited number of additional genes that are co-expressed with the disclosed genes, for example as evidenced by statistically meaningful Pearson and/or Spearman correlation coefficients, are included in a prognostic or predictive test in addition to and/or in place of disclosed genes.

Having described the invention, the same will be more readily understood through reference to the following Examples, which are provided by way of illustration, and are not intended to limit the invention in any way.

EXAMPLE 1 Gene Expression Analysis for Colon Cancer Recurrence

Methods and Materials:

Patients and Samples

Tumor tissue samples were from two cohorts of patients with stage II or stage III colon cancer treated with surgery alone form the basis for this report. Further details concerning the NSABP protocols C-01, C-02, C-03, and C-04 are available in C. Allegra, J Clin Oncology 21(2):241-250 (2003) and related U.S. application Ser. Nos. 11/653,102 and 12/075,813, the contents of which are incorporated herein by reference.

The first cohort pooled available patient samples from NSABP protocols C-01 or C-02 in which patients were randomly assigned to receive either colon resection alone or resection+bacillus Calmette-Guerin (“BCG”) immunotherapy. The second cohort (CCF) included stage II and stage III colon cancer patients treated with surgery alone at CCF between the years 1981 and 2000. None of the patients in either group received adjuvant chemotherapy. In both cohorts, gene expression measurements were obtained from archived, formalin-fixed, paraffin-embedded (FPE) colon tumor tissue.

Differential Expression Data:

The final number of evaluable FPE blocks was 270 in the NSABP cohort and 765 in the CCF cohort (n=1035). The primary reasons for exclusion were failure to meet minimum RNA yield (10% of samples in NSABP and 8% in CCF) and failure to meet quality control criteria for RT-qPCR (7% in NSABP and 2% in CCF).

The primary analysis in both studies investigated the relationship between the expression of 761 genes and RFI. This analysis identified sixty-five genes were found to be nominally significant in both studies. (See FIG. 1.) The high level of agreement was observed between the univariate hazard ratios for 63 (97%) of 65 genes significantly related to RFI in both studies. Of the genes found to be significantly related to RFI in either study, the majority were also related to both DFS and OS within the same study.

In both cohorts, the relationship between the expression of each gene and RFI was investigated, controlling for study and baseline characteristics. Any of the baseline clinical characteristics or study design attributes that had at least a modest association (p<0.2) with RFI were included in the multivariate analysis. Sixty-one (43%) of the 143 genes significant in univariate analyses in the NSABP cohort were statistically significant after controlling for nodal status, tumor location, tumor grade, mucinous tumor type, study protocol (C-01 vs. C-02), treatment assignment (BCG vs. none), and year of surgery. Eighty-eight (74%) of the 119 genes significant in univariate analysis in the CCF cohort retained significance after adjustment for age, nodal status, number of lymph nodes examined, tumor grade, mucinous tumor type, fixative, surgery year and T stage. There was agreement between the multivariate hazard ratios for the 65 genes significantly related to RFI in both studies. The hazard ratios were concordant for 63 of 65 genes. The consistency of hazard ratio estimates from the uni- and multivariate Cox regression analyses indicates that expression levels of these genes provide prognostic information which is relatively independent of traditional clinical predictors.

These 65 genes represent pathways that would be expected to be important in colon cancer recurrence. To identify genes that were co-expressed and therefore possibly members of the same functional gene family, hierarchical cluster analysis and forest plots were created using the genes that were significantly related to RFI in that study (not shown) as well as for the genes significantly related to RFI in both studies. Cluster analysis identified that the majority (48) of the prognostic genes fell into two relatively distinct gene groups: a stromal gene group (containing several subgroups) and a cell cycle gene group. The stromal group contained genes which, when highly expressed, were associated with a worse outcome and increased likelihood of recurrence, such as BGN, FAP, INHBA, and EFNB2. The cell cycle group contained genes which, when highly expressed, were associated with a better outcome and decreased likelihood of recurrence, such as cMYC, MYBL2, Ki-67, MAD2L1, and HSPE1.

EXAMPLE 2 Gene Expression Analysis for Prognostic and Predictive Genes

A study was conducted to assay gene expression levels in tumor samples obtained from patients with stage II or III colon cancer treated with surgery and 5FU/LV and perform analysis across four independent studies to identify genes that quantitate both the individual risk of recurrence in patients treated with surgery alone (prognosis) and the individual treatment benefit of 5-FU/LV adjuvant chemotherapy (prediction). Further information about these studies can be found in related U.S. application Ser. Nos. 11/653,102 and 12/075,813, the contents of which are incorporated herein by reference.

Methods and Materials

Patients and Samples

Tissue samples were obtained from two cohorts of patients with stage II or stage III colon cancer treated with surgery and 5FU/LV. The first cohort included available patient samples from the 5FU/LV arm of NSABP Study C-04 in which patients were randomly assigned to receive either 5FU/LV, 5FU+levamisole or 5FU/LV+levamisole. (See, N. Wolmark, et al., J Clin Oncol 17:3553-3559 (1999). The second cohort included available patient samples from the 5FU/LV arm of NSABP Study C-06 in which patients were randomly assigned to receive 5FU/LV or oral uracil/tegafur plus leucovorin. (See, B. Lembersky, et al., J Clin Oncol 24:2059-2064 (2006). The 5FU/LV regimen was the same in both studies. In both cohorts, gene expression measurements were obtained from archived, formalin-fixed, paraffin-embedded (FPE) colon tumor tissue.

Based on treatment assignment and eligibility in the original NSABP studies, 691 C-04 patients and 792 C-06 patients qualified for this study. Available formalin-fixed paraffin-embedded (FPE) blocks for patients enrolled in C-04 (n=360) and C-06 (n=573) were assayed. After applying pre-specified exclusion criteria, the final number of evaluable patients was 308 in the C-04 cohort and 508 in the C-06 cohort. The primary reasons for exclusion were failure to satisfy pathology requirements (8.6% in C-04 and 1.7% in C-06) and failure to meet clinical eligibility criteria (1.7% in C-04 and 7.5% in C-06).

Analysis Methods

The primary analysis in both studies investigated the relationship between the expression of each gene and RFI. This analysis identified 143 (19%) of the 761 genes as being significantly related to RFI in the C-04 cohort compared to 169 (45%) of the 375 genes in the C-06 cohort. Seventy-five genes were found to be nominally significant in both studies. The hazard ratios were concordant (i.e. in similar direction) for 73 (97%) of these 75 genes. Of the genes found to be significantly related to RFI in either study, the majority were also related to both DFS and OS within the same study. Seventy-one (50%) of 143 genes significantly associated with RFI in univariate analyses in the C-04 study were statistically significant after controlling for nodal status and age. One hundred thirty-seven (81%) of the 169 genes significant in univariate analyses in the C-06 study were statistically significant after controlling for nodal involvement and mucinous tumor type. A high level of agreement between the univariate and multivariate hazard ratios for genes significantly related to RFI in both studies was observed.

To identify prognostic genes across the four colon development studies, the focus was on the genes which significantly and consistently associated with RFI in both surgery only (C-01/C-02 and CCF studies described in Example 1) and surgery+5FU/LV-treated (C-04 and C-06) patients since prognostic genes are expected to have a similar relationship (i.e. similar direction and magnitude of the HR's) with outcome when measured in patients treated with the standard of care or in patients treated with a new intervention. A total of 48 (13%) of 375 genes studied in all four development studies were significantly (p<0.05) associated with RFI in both surgery only studies and at least one surgery+5FU/LV study. Due to type II error considerations, genes were not required to be significant in all four studies. The univariate hazard ratios and associated confidence intervals for the 48 genes in each of the four colon development studies are presented in FIG. 2. Cluster analysis identified two relatively distinct gene groups among the 48 prognostic genes: a stromal activation gene group (containing several subgroups) and a cell cycle gene group. The stromal group contained genes which, when highly expressed, were associated with a worse outcome and increased likelihood of recurrence, such as BGN, FAP, INHBA, and EFNB2. The cell cycle group contained genes which, when highly expressed, were associated with a better outcome and decreased likelihood of recurrence, such as cMYC, MYBL2, Ki-67, MAD2L1, and HSPE1.

In contrast to prognostic genes, the predictive genes are expected to exhibit a different relationship with outcome (i.e. different HR's) in patients treated with surgery only as compared to patients treated with surgery+5FU/LV. To identify predictive genes, multivariate Cox proportional hazards models were examined, including main effects of gene and treatment and an interaction of gene and treatment for each of the 375 genes pooling the data across the four colon development studies. A total of 66 (18%) of 375 genes studied in all four development studies had an interaction of gene expression and treatment significant at 0.10 level. Only 4 of these 66 genes had significant association with RFI in the two independent surgery alone studies and at least one of the surgery+5 FU/LV study (i.e. were included in the set of 48 prognostic genes), indicating that a small minority of predictive genes are both prognostic and predictive. Fifty-nine of the 66 genes were not associated with RFI in both surgery only studies, indicating that the majority of predictive genes are not also prognostic genes.

These 66 genes represent pathways that would be expected to be important in response to chemotherapy. Cluster analysis identified two relatively distinct gene groups among 66 potentially predictive genes. One group contains a large number of cell cycle related genes such as centromere and spindle associated proteins (CENPA, KIFC1, KIF22, STK15, MAD2L1, AURKB), checkpoint regulation (CDC2, BUB1), and a DNA topoisomerase (TOP2A). The second group contains genes which represent several different biological pathways, including a tight group of stromal activation genes (BGN, SPARC, COL1A1, CDH11, MMP2, and TIMP1), and genes associated with apoptosis (BIK), 5FU metabolism (UPP), and B-catenin/wnt signaling (AXIN2, LEF). It is of note that the two mismatch repair genes (MSH2 and MSH3) and several hypoxia/stress response genes (NR4A1, RhoB, HIF1A, CREBBP, PKR2, EPAS1) were also associated with response to 5-FU/LV chemotherapy.

Preliminary prognostic models were built using subsets of the 48 prognostic genes. The results from a representative model containing 10 prognostic genes are shown in FIGS. 3a and 3b for stage II and stage III patients, respectively, treated with surgery only (C-01/C-02 and CCF cohorts). Patients were divided into three equally sized groups based on the calculated Recurrence Score. This model separated the 628 Stage II patients into groups with low, intermediate and high risk of recurrence: the lowest tertile had a 5% (95% CI 3%, 9%) risk of recurrence at 3 years vs. 14% (10%, 20%) and 22% (16%, 28%), respectively, for the middle and highest tertiles. (See, FIG. 4a.) For 395 Stage III patients, the two lowest tertiles had 26% (19%, 35%) and 26% (19%, 34%) risk of recurrence at 3 years vs. a 47% (39%, 56%) risk for the highest tertile. (See FIG. 4b.) For comparison, the overall 3-year risks of recurrence of Stage II and Stage III patients were 13% and 33%, respectively. When bootstrap was applied, the average Kaplan-Meier estimates (and associated 95% confidence intervals) of recurrence rates at 3 years for stage II patients were 5% (2%, 9%), 12% (8%, 17%) and 22% (18%, 27%) for the 1st, 2nd and 3rd tertile, respectively. For stage III patients, the corresponding estimates were 23% (16%, 30%), 28% (19%, 37%) and 48% (40%, 56%), respectively.

EXAMPLE 3 Validation of Algorithm-Based Molecular Diagnostic Assay

After the 65 prognostic and 66 predictive gene candidates were identified, the genes were examined further for consistency in association between gene expression and RFI (prognosis) and differential relationship between with RFI in treated vs. untreated patients (prediction) across the four colon development studies using univariate and multivariate Cox proportional hazards models. Representation of the relevant biologic pathways, distribution of gene expression, functional form of the relationship between gene expression, and RFI and analytical performance of individual genes were also taken into account.

Forest plots for the predictive genes (after thresholding) were reviewed and genes were identified that (1) displayed predictive effects either in both Stage II and Stage III colorectal cancer, or in Stage III only; (2) had significant (e.g., p<0.10) gene by treatment interaction in a model of gene (n=9) or median Ct<4 (n=2); and (3) had significant (p<0.10) gene by treatment interaction after RSu and TRT were forced into the model. Genes with consistent univariate hazard ratios (HRs) were preferred. In addition, forest plots for the predictive genes were examined qualitatively and genes displaying predictive effects either in both Stage II and Stage III colorectal cancer, or in Stage III only were identified. Through this analysis the following additional 10 predictive gene candidates were identified (in addition to the 6 predictive genes in the final algorithm): RANBP2, BUB1, TOP2A, C20_ORF1, CENPF, STK15, AURKB, HIF1A, UBE2C, and MSH2. Based on these results, multi-gene models were designed and analyzed across all four studies. Those analyses, together with a methodical evaluation of analytical performance of each candidate gene, led to the design of a multi-gene RT-PCR-based clinical assay to predict recurrence risk and treatment benefit from 5FU/LV. The genes represent biological categories that are important in colon cancer: stromal group (BGN, FAP, INHBA, EFNB2), cell cycle group (Ki-67, MYBL2, cMYC, MAD2L1, HSPE1), cell signaling (GADD45B), apoptosis group (BIK), transcription factor group (RUNX1), and MSI group (AXIN2), as well as 5 reference genes (ATP5E, GPX1, PGK1, UBB, VDAC2) for normalization of gene expression.

Methods and Materials

Patients and Samples

The developed algorithm may be validated using samples obtained from the QUASAR study. The QUASAR Collaborative Group trial is the largest reported single randomized study of observation versus adjuvant chemotherapy in patients with resected stage II colon cancer. (See, Lancet 370:2020-2029 (2007).) In that study, patients with resected stage II and III colon and rectal cancer were assigned by treating physicians to one of two arms of the study based on either a “clear” or “uncertain” indication for adjuvant therapy. In the “clear” arm, all patients (n=4320) received adjuvant 5-FU/leucovorin (LV) chemotherapy with or without levamisole. In the “uncertain” arm, patients (n=3239) were randomized to either observation (n=1617) or adjuvant 5-FU/LV chemotherapy (n=1622). As expected, the “clear” arm enrolled primarily stage III patients (70%), and the “uncertain” arm enrolled a high proportion of stage II patients (91% stage II, 71% colon cancer).

These results from QUASAR demonstrate that adjuvant 5-FU/LV treatment benefits a small but significant subset of stage II colon cancer patients. (See, e.g., FIG. 5.) Nevertheless, the physician managing stage II colon cancer still faces considerable challenges, including the fact that the majority of such patients are cured with surgery alone and that adjuvant 5-FU/LV chemotherapy carries potential toxicities of leucopenia, stomatitis, and diarrhea. Clearly, the decision to administer adjuvant 5-FU/LV chemotherapy would be greatly aided by the ability to identify reliably: 1) patients who are likely to be cured with surgery alone and 2) patients who are at substantial risk of recurrence following surgery and have a significant likelihood of clinical benefit with adjuvant treatment. With regard to the latter, it is worth emphasizing that the clinically relevant information for patients and oncologists includes not only the magnitude of the baseline risk of recurrence but also the magnitude of potential benefit (i.e. the absolute clinical benefit) associated with adjuvant 5-FU/LV treatment.

The validation study entailed the use of a pre-specified RT-PCR-based 18-gene clinical assay (see genes listed in Table 3) applied to archival paraffin-embedded tumor tissue specimens from colon cancer patients studied in QUASAR. The study considered the relationship between (1) a continuous RS and recurrence risk in patients randomized to surgery alone, and compared to that of patients randomized to surgery followed by adjuvant 5-FU/LV chemotherapy (controlling for simultaneous prognostic effects of clinical and pathological covariates); and (2) a continuous TS and chemotherapy benefit in patients randomized to surgery alone or surgery followed by adjuvant 5-FU/LV chemotherapy. The study compared the risk of recurrence between the high and low recurrence risk groups based on pre-specified cut-points for RS. A two-fold higher recurrence risk at 3 years in the high recurrence risk group compared to the low recurrence risk group was considered clinically significant. Alternative clinical endpoints, including RFI, DFS and OS, were considered. The study also looked for a significant (1) trend in absolute chemotherapy benefit for recurrence at 3 years across the low, intermediate, and high chemotherapy benefit groups; (2) interaction between the continuous TS and treatment relative to alternative clinical endpoints, including RFI, OS and DFS; (3) interaction between MMR status and treatment after controlling for the prognostic effects of the continuous RS and prognostic covariates.

Fixed paraffin-embedded colon tumor tissue from approximately 1,500 patients from QUASAR with stage II colon cancer. The RNA was extracted from the tumor tissue and RT-PCR analysis was conducted to determine expression levels of 13 cancer-related and 5 reference genes (Table 3). A prospectively-defined algorithm was used to calculate a RS and TS for each patient. Patients were classified into low, intermediate, and high recurrence risk groups using the RS and pre-specified cut-points (Table 1). Similarly, patients were classified into low, intermediate, and high chemotherapy benefit groups based on the combination of the RS and TS and on pre-specified cut-points (Table 2). These cut-points define the boundaries between low and intermediate benefit groups and between intermediate and high benefit groups.

The specimens were also assessed by pathology to determine: tumor type, tumor grade, presence of lymphatic and/or vascular invasion, number of nodes examined, depth of invasion (pathologic T stage), MMR status, and other QC metrics. This information was used to determine whether there was a significant relationship between risk of recurrence and individual and pathologic covariates.

Expression levels of 13 cancer-related genes used in the calculation of the RS and TS were reported as values from the RT-PCR assay. Gene expression measurements were normalized relative to the mean of five reference genes (ATP5E, GPX1, PGK1, UBB, VDAC2). For each cancer-related gene, a cycle threshold (CT) measurement was obtained by RT-PCR, and then normalized relative to a set of five reference genes. Reference-normalized expression measurements typically range from 0 to 15, where a one unit increase generally reflects a 2-fold increase in RNA quantity.

Analysis Methods:

Unless otherwise stated, all significance tests were conducted at the 0.05 significance level, and two-sided p-values and confidence intervals will be reported. To preserve the overall family-wise error rate for testing the primary objectives at the 0.05 significance level, the analysis applied conditional fixed sequential testing. A Cox proportional hazards regression model was fit to the clinical endpoint RFI for the patients who were randomized to surgery alone and a likelihood ratio test used to determine if the RS is significantly associated with the risk of recurrence (i.e. if the hazard ratio associated with the RS is significantly different from 1).

A Cox proportional hazards regression was used to model the first 3 years of follow-up data, that is, censoring time to recurrence at 3 years after randomization for patients who have not experienced a recurrence before that time, to determine if the TS is associated with the magnitude of chemotherapy benefit. The likelihood ratio test was used to compare the reduced model with RS, TS and the treatment main effect, with the full model that includes RS, TS, the treatment main effect, and the interaction of treatment and TS. In addition, we will use the method of Royston and Parmar (2002) to fit a flexible parametric model to RFI using all available follow-up data. The method will model the hazard of recurrence using the Weibull distribution with natural spline smoothing of the log cumulative hazards function, with effects for treatment (chemotherapy or observation), RS, TS and the interaction of TS with treatment, allowing the effects of treatment, RS, TS and TS interaction with treatment to be time dependent. The predicted effect of chemotherapy as a function of TS will be estimated at follow-up times of 2, 3, and 5 years.

Power calculations were carried for the Cox proportional hazards model with a single non-binary covariate using the method proposed by Hsieh and Lavori (2000) as implemented in PASS 2008. One skilled in the art would recognize that power at alpha 0.01-0.05 alpha would be sufficient to control for type I error.

For example, a test comparing a reduced Cox proportional hazards regression model of gene expression and treatment to a full model containing gene expression, treatment and interaction of gene expression and treatment indicated an association of chemotherapy benefit and expression of RUNX1 (p=0.030, Interaction HR=0.59, HR 95% CI (0.37, 0.95) and FAP (p=0.065, Interaction HR=0.66, HR 95% CI (0.42, 1.03).

The association of gene expression and recurrence risk in surgery alone patients was examined for the 13 cancer-related genes. Multivariate Cox proportional hazards regression model allows estimation of recurrence risk adjusted for a specific distribution of clinical covariates. Recurrence risk estimates were produced from this multivariate model, adjusting for distribution of clinical covariates, differences in distribution in various study populations (if any), and baseline survival.

Table 8 presents the results of the univariate Cox proportional hazards regression models of gene expression on RFI. FIG. 12 demonstrates the group risk (by Kaplan Meier curve) for Stage II colon cancer patients following surgery based on risk of recurrence at three years and recurrence score (including stromal and cell cycle group genes). FIG. 13 demonstrates the risk profile plot (by Kaplan Meier curve) for risk of recurrence at five years (QUASAR—surgery only) and recurrence score (including stromal, cell cycle, and (for RS2) apoptosis genes).

In addition, the analyses combining the results from the four colon development studies and the QUASAR validation study were carried out to assess the performance of the 13 cancer-related genes across more than 3000 patients. Two different analysis methods were applied to combine the results across studies: (1) meta-analysis treating inter-study variation as random using the method of Paule and Mandel (1982) as implemented by DerSimonian and Kacker (2007); and (2) Cox proportional hazards regression model stratified by study, stage and treatment. Table 9 presents the results of these analyses. As can be observed, all but AXIN were shown to be associated with risk of recurrence in colon cancer (i.e. 95% CI did not include 1). (See, e.g., R. Paule, J. Mandel, Journal of Research of the National Bureau of Standards 87:377-385 (1982); R. der Simonian and R. Kacker, Cotemp. Clin Trials 28:105-144 (2007), both incorporated herein by reference.)

EXAMPLE 4 Alternative Algorithm-Based Assay

Further analysis of data from the studies outlined in the Examples above suggested that incorporating additional genes into the Recurrence Score gene panel may yield improved performance. For example, BIK and EFNB2 were significantly associated with recurrence risk in both surgery alone and 5FU-treated patients. Statistical modeling was conducted to explore the strength of association between several multi-gene modules and recurrence of colon cancer. Table 10 and FIGS. 17-19 demonstrate comparative prognostic performance of selected multi-gene models.

Table 10: Multi-gene models based on standardized gene expression.

TABLE 10 SCORE STD LR Genes N Variable N HR Chisq Est StdHR LRChisq LRPVal 1 BGN 3137 1.57 140.2 0.09 1.09 1.13 0.29 FAP −0.09 0.91 1.93 0.16 INHBA 0.10 1.11 2.29 0.13 EFNB2 0.19 1.22 26.02 3.4E−07 GADD45B 0.02 1.02 0.16 0.69 Ki-67 −0.13 0.88 6.37 0.01 MAD2L1 −0.13 0.88 6.35 0.01 BIK −0.15 0.86 12.91 3.3E−04 cMYC −0.13 0.88 9.10 0.003 MYBL2 −0.02 0.98 0.25 6.2E−01 2 BGN + INHBA + FAP + 3137 1.52 120.7 0.07 1.23 19.85 8.4E−06 EFNB2 GADD45B −0.02 0.98 0.13 0.72 Ki-67 + MAD2L1 + −0.13 0.77 39.19 3.8E−10 BIK cMYC −0.10 0.91 5.50 0.02 MYBL21 −0.01 0.99 0.10 0.75 3 BGN + INHBA + FAP + 3137 1.51 118.9 0.06 1.22 25.61 4.2E−07 EFNB2 + ⅓ GADD45B Ki-67 + MAD2L1 + −0.12 0.74 54.97 1.2E−13 BIK + ¾cMYC + ½ MYBL2 4 BGN + INHBA + FAP + 3137 1.51 119.6 0.06 1.21 24.60 7.1E−07 EFNB2 + ⅓ GADD45B Ki-67 + MAD2L1 + −0.13 0.74 55.61 8.8E−14 BIK + ½cMYC + ½ MYBL2

Based on the statistical modeling, it was determined that a multi-gene model using BGN and Ki-67, or BGN, Ki-67 and BIK, can provide minimal prognostic information to colon cancer patients. See FIG. 18-19. However, a model consisting of ten prognostic genes (BGN, FAP, INHBA, EFNB2, GADD45B, Ki-67, MAD2L1, BIK, cMYC, MYBL2), plus reference genes (“RS2”), provided a highly accurate assessment of risk of recurrence in colon cancer. See FIG. 20.

EXAMPLE 5 Identifying Co-Expressed Genes and Gene Cliques

Gene cliques that co-express with the validated prognostic and predictive genes are set forth in Tables 4-6. These gene cliques were identified using the method described herein.

Materials and Methods:

Microarray data for colon tumor samples may be obtained internally, or derived from a public database, such as Gene Expression Omnibus (GEO). Microarray data was normalized and a pairwise Spearman correlation matrix computed for all array probes. Significant co-expressed probes across different studies was filtered out, and a graph built to compute probe cliques, map the probes to genes, and generate the gene cliques.

Download Colon Cancer Microarray Datasets

Five datasets from the Gene Expression Omnibus (GEO) database were used to compute the colon cliques. These datasets were identified as colon tumor expression experiments using the Affymetrix® HG-U133A microarray chip (Affimetrix Inc., Santa Clara, Calif.). Detailed information regarding the GEO database can be found at the National Center for Biotechnology Information (NCBI) website. Table 7 provides the accession number for the Geo datasets and the number of tumor samples in each dataset.

Array Data Normalization

The array data from GEO may be normalized using appropriate software, e.g. Affymetrix MAS5.0, or an open source RMA software like the bioconductor package.

If the sample array data are of MAS5.0 type, they are normalized with the following steps:

    • 1. Expression level is changed to “10” if the value is <10.
    • 2. Expression level is then log transformed.
    • 3. Median is computed on the log transformed values for the whole array probes.
    • 4. Each probe value subtracts the median and the resulting value will be defined as normalized value

If the sample array data are of RMA type, they are normalized with the following steps:

    • 1. Median is computed on the RMA generated values for the whole array probes.
    • 2. Each probe value subtracts the median and the resulting value will be defined as normalized value

Array Probe Co-Expression Pair Generation

The Spearman's rank correlation coefficient (rs) was calculated for every unique pair of probes in the dataset (22283 probes resulting 248,254,903 unique pairs for each dataset). These pairs were then filtered by a significant threshold value T; any probe pair which has an rs>=T was considered significant. Significant correlation pairs (had Spearman correlation values above threshold) were generated for each GEO dataset. For a given seeding gene probe, if the significant pairs involving the seeding probe or its directly connected probes existed across all five GEO datasets, they were placed in a graph and used to calculate maximal cliques.

Array Probe Clique Generation

The Brön-Kerbosch algorithm was used to generate the maximal cliques from a graph of significant probe pairs generated from the above step. First, three “sets” of nodes were created. The first set, compsub, was the set to be extended or shrunk on traveling along a branch of the backtracking tree. The second set, candidates, was the set of all points that will be added to compsub. The third set, not, was the set of nodes already added to compsub. The recursive mechanism for generating cliques is as follows:

    • 1. Selection of a candidate node.
    • 2. Adding the selected candidate node to compsub.
    • 3. Creating new sets candidates and not from the old sets by removing all nodes not connected to the selected candidate, keeping the old sets in tact.
    • 4. Calling the extension operator to operate on the sets just formed.
    • 5. Upon return, removal of the selected candidate from compsub and its addition to the old set not.

If after the extension operator, the candidates and not sets were empty, then the nodes on compsub were a clique and the mechanism starts over with a new candidate node. (See FIG. 11.)

Gene Clique Reporting

After the probe cliques had been computed, each probe in the cliques was mapped to genes as identified by Entrez Gene Symbol (Official Gene Symbol). Table 6 lists the report for the cliques associated with FAP, INHBA, Ki-67, HSPE1, MAD2L1, and RUNX1.

Certain probes have multiple mapping to Genes. They are listed as the same AffyProbeID within a SeedingGene but have multiple ambiguous map to Official Genes (listed as CliquedGene column). Certain CliquedGenes are listed as “---” in Table 6. That means the AffyProbes do not map to any current Official Genes. The weight column list out the weight as we merged cliques. It is essentially is the number of clique evidence for coexpression with the seeding gene.

EXAMPLE 6 Use of Thresholding

Thresholding can be used to improve the reproducibility in recurrence score (RS) and treatment score (TS) reporting by accounting for significant losses in precision as gene expression measurements approach the limit of quantitation (LOQ) of the assay. The LOQ of an assay represents the lowest concentration of RNA at which results can reliably be reported and have been estimated for each of the 18 colon cancer genes.

As an example, FIG. 26 shows the effects of diluting RNA concentration on (non-normalized) gene expression (Ct) measurements of Ki-67. The variance in Ct measurement clearly increases as RNA concentration decreases. In fact, it may be shown that the log variance in Ct measurement is roughly proportional to the mean Ct measurement for a gene. As a consequence, the variability in RS and TS may be further reduced by truncating gene expression measurements at or near the LOQ, thereby reducing the potential for noise being introduced into RS and TS estimation.

EXAMPLE 7 Calculating Gene Expression: Tumor Region Ratios

The clinical development studies in stage II/III colon cancer described above illustrated that genes which are frequently associated with stroma are correlated with increased risk of recurrence, whereas cell cycle genes are correlated with decreased risk of recurrence. This fact may account for the variability of RS/TS scores, and could be taken into account if the algorithm described herein considered the amount of stroma and luminal area, as well as localized gene expression in these regions. For example, an algorithm taking into account the ratios of stromal gene expression values per stroma area unit, and cell cycle gene expression values per epithelial area unit, would increase the precision and reproducibility of a recurrence risk prediction by decreasing heterogeneity within tumor blocks for a given patient.

A study was conducted to clarify the impact of variable tumor region areas and stromal/cell cycle gene expression on recurrence risk. RNA was extracted from different regions of colon tumors—the luminal part of the tumor and the tumor-associated stroma. FIG. 14 shows that there are higher expression levels of the stromal genes in the tumor-associated stroma and higher expression levels of the cell cycle genes in the luminal part of the tumor. It is therefore likely that the stroma is contributing significantly to the stromal group score (SG or SGS) and the epithelia is significantly contributing to the cell cycle gene score (CCG or CCGS). Given these assumptions, the area of stroma within the sample contributes to the variability of the SG (within and between blocks) and therefore the score(s). Similarly, the area of epithelia within the sample analyzed could contribute to the variability of the CCG (within and between blocks) and therefore the score(s).

Gene expression within tumor epithelia cells and stroma varies from patient to patient. For example, FIG. 15 demonstrates that some patients may have higher levels of gene expression in their tumor-associated stroma for stromal genes than do other patients. Thus, some patients can have large amounts of stroma but low activity, whereas other patients can have smaller amounts of stroma but high activity. In addition, gene expression levels for the same patient can vary depending on the location of the tumor (e.g., within and between tumor blocks). This variability can impact reproducibility of recurrence and treatment scores for a patient. For example, FIG. 16 demonstrates the variability, by tissue section of the same tumor block, of stromal group score (SG), cell cycle group score CCG), cell signaling group (CSG or GADD45B), and recurrence score (RS). This analysis was done on multiple sections from the same tumor block, and included data from 11 patients.

Therefore, taking into account the area of the tumor-associated stroma and the area of the tumor-luminal regions in calculating the RS algorithm and in calculating the TS algorithm can enhance the reproducibility of the RS and TS, respectively, thus leading to greater accuracy of recurrence risk prediction.

For example, the expression level of stromal group genes can be provided as a ratio of the expression level of one or more stromal group genes to the tumor-associated stroma unit area (“sua”) assayed. In another example, the expression level of cell cycle group genes can be provided as a ratio of the expression level of one or more cell cycle group genes to the tumor epithelial unit area (“cua”) are assayed. The RS algorithm could be modified in the following form: RS=[(SG×sua coefficient)±(CCG×sua coefficient)]+[(SG×cua coefficient)±(CCG×cua coefficient)]±(repeat analysis for other gene groups, e.g., CSG, AG, and/or TFG). Similarly, the TS algorithm could be modified in the following form: TS=[(SG×sua coefficient)±(CCG×sua coefficient)]+[(SG×cua coefficient)±(CCG×cua coefficient)]±(repeat analysis for other gene groups, e.g., AG, TFG, and/or MG.)

In addition, the following exemplary algorithm provides a method to analyze and remove variability associated with gene expression in different portions of the block. For example, for cell cycle and stromal gene expression in different portions of a tumor block one could calculate: SGSij=SGi+SBij (Stromal gene group value for subject i block j is sum of a Gene effect and a Block effect) and CCGSij=CCGi+CCBij (Cell cycle gene group value for subject i block j is sum of a Gene effect and a Block effect).

SGS and CCGS are not correlated across subjects: SGS and CCGS variability is mostly from SG and CCG, the gene expression factor, and these are not correlated.

SGS and CCGS are correlated within subjects: There is a common effect underlying CCB and SB. Calculate: SGSrij=SGSij−SGSi=SBij−SBi.
CCGSrij=CCGSij−CCGSi.=CCBij−CCBi.

Correlation between SGSrij and CCGSrij can be thought of as a within subjects correlation pooled across subjects, i.e. an average within patient correlation. An informal approach to estimating ρ in (Yij, Xij)˜N((μyi, μxi), [σy, ρyx//ρyx, σx]). Alternatively could assume Yij=αi+βXij+εij

If % Stroma correlates with the SGS within subject, it could provide a means of removing this source of variability in the RS and/or TS values.

EXAMPLE 8 Stromal Risk Analysis

Methods and Materials

A study involving 444 patients from a subset of the Cleveland Clinic Foundation (CCF) cohort described in Example 1 was conducted to clarify how the amount of tumor-associated stroma (“stroma area”) in a colon cancer tumor sample impacts the recurrence risk for stage II/III colon cancer patients (“Stromal Risk”). Specifically, a subset of the CCF cohort (cohort-sampling study design) involving all 148 recurrences from the CCF cohort and a random sample of approximately twice as many (i.e., 296) non-recurrences was used, resulting in 444 patients treated by resection of the colon.

Inclusion criteria included:

    • Either stage II or stage III colon cancer patient.
    • Patient treated with colon resection (surgery) at CCF between the years of 1981 and 2000.

Exclusion criteria included:

    • No tumor block available from initial diagnosis in the CCF archive.
    • No tumor or very little tumor (<5% of the area occupied by invasive cancer cells compared to the area occupied by other epithelial elements, such as normal epithelium, or lymphatic) in block as assessed by examination of the H&E slide by the CCF and Genomic Health Pathologist.
    • Patients diagnosed with stage II or stage III signet ring colon cancer (WHO classification)
    • Insufficient RNA (<586 ng) for RT-PCR analysis.
    • Average non-normalized CT for the 5 reference genes≥35.

The full CCF cohort included a total of 886 FPE tumor tissue blocks. Of these, 108 were excluded due to failure to satisfy pathology and/or laboratory requirements described below. An additional 13 patients were excluded after the laboratory, pathology and clinical data were merged because of failure to satisfy all study inclusion and exclusion criteria, leaving 765 evaluable patients. The initial histological assessment by a Genomic Health pathologist was to evaluate the slide for the quantity of tumor and, where necessary, mark for manual micro dissection to enrich the tumor region. In this initial pathology review 8 cases were found to have insufficient tumor tissue (<5% tumor tissue) and thus failed the initial pathology review. The samples then underwent full histology review. Grade was captured by CCF and Genomic Health pathologists and each pathology read was analyzed separately (i.e. no attempt was made to create a ‘combined’ pathology score). An additional 11 cases failed this full pathology review due to the presence of a signet ring morphology comprising greater than 50% of the invasive component, lack of sufficient invasive tumor tissue (<5% cancer cells) or tissue type other than colon. Patient and sample disposition from the CCF study are summarized in Table 11.

TABLE 11 Patient Disposition from CCF Study Category N Patients % Patients Patients with available blocks 886 100%  Excluded due to: 121 13.7%  Failed pathology review 18 2.0% Insufficient RNA 73 8.2% QC of RT-PCR (incomplete or poor 17 1.9% data quality) Failure to satisfy all clinical 13 1.5% eligibility criteria* Evaluable patients 765 86.3% 

All 444 evaluable samples underwent both standard and digital pathology assessments. Using the 120-slide capacity ScanScope XT system, automated scanning of all study H&E slides were conducted at 20× scanning magnification with autopopulation of patient identification fields with barcode data using the Spectrum information management system. The 20× scanning magnification was selected because this magnification gives superior optimization of image quality and scanning speed.

Digital H&E scans were obtained from the Aperio® Digital Pathology System. Two different software systems—the Aperio® Genie Digital Pathology Image Analysis software and the Definiens® Digital Pathology Image Analysis software—were used to generate digital H&E measurements. The Definiens image analysis software, based on the Definiens Cognition Network Technology®, examines pixels in context and builds up a picture iteratively, recognizing groups of pixels as objects.

The pathologist and assistant trained the image analysis applications to detect regions of interest (e.g., mucin, tumor glands and tumor stroma) using previously captured digital images of the entire enriched tumor portion. These training slides were representative of the slides to be assessed by the Aperio system. Several variations of the two image analysis algorithms were developed for low and high grade carcinomas and mucinous carcinomas. These were developed by identification of regions of interest, and then having the programs “learn” from the training slides. The resulting algorithms were applied to the entire patient cohort, analyzing the enriched tumor portions of the patient samples. The patient samples were batched into three digital study sets (i.e., low grade, high grade and mucinous carcinomas) as determined by the GHI pathologist and all images were processed using batch processing.

Findings and Statistical Analysis

The surface area of tumor-associated stroma varies from patient to patient. For example, FIG. 21 provides a variability plot for natural logarithm of stroma area, as measured by the Aperio digital pathology system, for the 444 patients under study, stratified by recurrence-free interval status.

Statistical analyses were performed to determine if there was a significant relationship between stroma area and recurrence-free interval (RFI) Specifically, we compared the (reduced) Weighted Cox Proportional Hazards model for RFI based on the main effect for tumor stage (Stage II and Stage III), versus the (full) Weighted Cox Proportional Hazards model for RFI based on the main effects of tumor stage and stroma area as measured by the Aperio digital image analysis system. Weighted Pseudo Partial Likelihood approach was used to accommodate the use of a case-cohort sampling study design. A Wald test for the hypothesis that the hazard ratio for stroma area is 1 versus the 2-sided alternative hypothesis that the hazard ratio is not 1 was performed. The resulting Wald χ2=15.64 with 1 degree of freedom resulting in a 2-sided p-value <0.001, indicating that stroma area is prognostic of disease recurrence (beyond tumor stage alone) in colon cancer patients treated with colon resection. The resulting standardized hazard ratio for stroma area is 1.45, indicating that there is a 45% increase in the relative risk for disease recurrence for each standard deviation increase in stroma area.

TABLE 12 Proportional Hazard Regression for Recurrence-Free Interval: Stage and Stroma Area Alone PH Regression on RFI for Stage, Stroma Area Alone Robust HR Wald Variable Coef SE HR 95% CI DF ChiSq P value Stage (III vs II) 0.66 0.19 1.94 (1.34, 2.82) 1 12.27 <.001 Standard Area - 0.37 0.09 1.45 (1.20, 1.74) 1 15.64 <.001 Stroma Area, Aperio

In addition to testing if stroma area is prognostic of disease recurrence, statistical analyses were performed to determine if stroma area provides additional prognostic information beyond both stage and Recurrence Score. Specifically, we compared the (reduced) Weighted Cox Proportional Hazards model for RFI based on the main effect for stage (Stage II and Stage III) and Recurrence Score, versus the (full) Weighted Cox Proportional Hazards model for RFI based on the main effects of tumor stage, Recurrence Score and stroma area as measured by the Aperio digital image analysis system. A Wald test for the hypothesis that the hazard ratio for stroma area is 1 versus the 2-sided alternative hypothesis that the hazard ratio is not 1 was performed. The resulting Wald ratio χ2=13.17 with 1 degree of freedom resulting in a 2-sided p-value <0.001, indicating that stroma area is prognostic of disease recurrence beyond tumor stage and Recurrence Score. The resulting standardized hazard ratio for stroma area is 1.41, indicating that there is a 41% increase in the relative risk for disease recurrence for each standard deviation increase in stroma area.

TABLE 13 Proportional Hazard Regression for Recurrence-Free Interval: Stage, Stroma Area and Recurrence Score PH Regression on RFI for Stage, Stroma Area Alone, and R2 Robust HR Wald Variable Coef SE HR 95% CI DF ChiSq P value Stage (III vs II) 0.65 0.19 1.88 (1.32, 2.81) 1 11.49 <.001 Standard Area - 0.34 0.10 1.44 (1.17, 1.70) 1 13.17 <.001 Stroma Area, Aperio RS2/25 0.57 0.19 1.46 (1.122, 2.55) 1 9.19 0.002

Similar analyses were performed to test if stroma area provides additional prognostic information beyond both stage and RS2. Specifically, we compared the (reduced) Weighted Cox Proportional Hazards model for RFI based on the main effect for stage (Stage II and Stage III) and RS2, versus the (full) Weighted Cox Proportional Hazards model for RFI based on the main effects of tumor stage, RS2 and stroma area as measured by the Aperio digital image analysis system. A Wald test for the hypothesis that the hazard ratio for stroma area is 1 versus the 2-sided alternative hypothesis that the hazard ratio is not 1 was performed. The resulting Wald ratio χ2=14.86 with 1 degree of freedom resulting in a 2-sided p-value <0.001, indicating that stroma area is prognostic of disease recurrence beyond tumor stage and RS2. The resulting standardized hazard ratio for stroma area is 1.44, indicating that there is a 44% increase in the relative risk for disease recurrence for each standard deviation increase in stroma area.

TABLE 14 Proportional Hazard Regression for Recurrence-Free Interval: Stage, Stroma Area and RS2 PH Regression on RFI for Stage, Stroma Area Alone, and RS2 Robust HR Wald Variable Coef SE HR 95% CI DF ChiSq P value Stage (III vs II) 0.63 0.19 1.88 (1.29, 2.74) 1 10.87 <.001 Standard Area - 0.36 0.09 1.44 (1.19, 1.73) 1 14.86 <.001 Stroma Area, Aperio RS2/25 0.38 0.12 1.46 (1.15, 1.85) 1 9.79 0.002

For analysis purposes, stroma area can be stratified into low and high Stroma Risk Groups. Specifically, we define low risk (stroma score ≤0) and high risk (stroma score >0) where stroma score=(stroma area−mean)/standard deviation. Kaplan-Meier Plots for Stage II and Stage III patients stratified by Stroma Risk Group, provided in FIGS. 22 and 23 respectively, clearly show separation between risk groups (Logrank p-value <0.01). Similarly, Kaplan-Meier Plots for Stage II and Stage III patients stratified by both Stroma Risk Group and Recurrence Score Risk Group, provided in FIGS. 24 and 25 respectively, show even greater separation between risk groups (Logrank p-value <0.01).

CONCLUSION

These analyses show that stroma area is independently prognostic of disease recurrence in stage II and stage III patients and that RS, stromal area, and nodal status all provide important prognostic information in stage II and III colon cancer. The discovery that it is surface area of tumor-associated stroma that is most strongly associated with risk of recurrence, rather that proportional measurements of tumor regions, was an unexpected result of this study.

TABLE A Gene Accession Reagt Sequence SEQ ID NO A-Catenin NM_001903.1 FPr CGTTCCGATCCTCTATACTGCAT SEQ ID NO: 1 Probe ATGCCTACAGCACCCTGATGTCGCA SEQ ID NO: 2 RPr AGGTCCCTGTTGGCCTTATAGG SEQ ID NO: 3 ABCB1 NM_000927.2 FPr AAACACCACTGGAGCATTGA SEQ ID NO: 4 Probe CTCGCCAATGATGCTGCTCAAGTT SEQ ID NO: 5 RPr CAAGCCTGGAACCTATAGCC SEQ ID NO: 6 ABCC5 NM_005688.1 FPr TGCAGACTGTACCATGCTGA SEQ ID NO: 7 Probe CTGCACACGGTTCTAGGCTCCG SEQ ID NO: 8 RPr GGCCAGCACCATAATCCTAT SEQ ID NO: 9 ABCC6 NM_001171.2 FPr GGATGAACCTCGACCTGC SEQ ID NO: 10 Probe CCAGATAGCCTCGTCCGAGTGCTC SEQ ID NO: 11 RPr GAGCTGCACCGTCTCCAG SEQ ID NO: 12 ACP1 NM_004300.2 FPr GCTACCAAGTCCGTGCTGT SEQ ID NO: 13 Probe TGATCGACAAATGTTACCCAGACACACA SEQ ID NO: 14 RPr GAAAACTGCTTCTGCAATGG SEQ ID NO: 15 ADAM10 NM_001110.1 FPr CCCATCAACTTGTGCCAGTA SEQ ID NO: 16 Probe TGCCTACTCCACTGCACAGACCCT SEQ ID NO: 17 RPr GGTGATGGTTCGACCACTG SEQ ID NO: 18 ADAM17 NM_003183.3 FPr GAAGTGCCAGGAGGCGATTA SEQ ID NO: 19 Probe TGCTACTTGCAAAGGCGTGTCCTACTGC SEQ ID NO: 20 RPr CGGGCACTCACTGCTATTACC SEQ ID NO: 21 ADAMTS12 NM_030955.2 FPr GGAGAAGGGTGGAGTGCAG SEQ ID NO: 22 Probe CGCACAGTCAGAATCCATCTGGGT SEQ ID NO: 23 RPr CAGGGTCAGGTCTCTGGATG SEQ ID NO: 24 ADPRT NM_001618.2 FPr TTGACAACCTGCTGGACATC SEQ ID NO: 25 Probe CCCTGAGCAGACTGTAGGCCACCT SEQ ID NO: 26 RPr ATGGGATCCTTGCTGCTATC SEQ ID NO: 27 AGXT NM_000030.1 FPr CTTTTCCCTCCAGTGGCA SEQ ID NO: 28 Probe CTCCTGGAAACAGTCCACTTGGGC SEQ ID NO: 29 RPr ATTTGGAAGGCACTGGGTTT SEQ ID NO: 30 AKAP12 NM_005100.2 FPr TAGAGAGCCCCTGACAATCC SEQ ID NO: 31 Probe TGGCTCTAGCTCCTGATGAAGCCTC SEQ ID NO: 32 RPr GGTTGGTCTTGGAAAGAGGA SEQ ID NO: 33 AKT1 NM_005163.1 FPr CGCTTCTATGGCGCTGAGAT SEQ ID NO: 34 Probe CAGCCCTGGACTACCTGCACTCGG SEQ ID NO: 35 RPr TCCCGGTACACCACGTTCTT SEQ ID NO: 36 AKT2 NM_001626.2 FPr TCCTGCCACCCTTCAAACC SEQ ID NO: 37 Probe CAGGTCACGTCCGAGGTCGACACA SEQ ID NO: 38 RPr GGCGGTAAATTCATCATCGAA SEQ ID NO: 39 AKT3 NM_005465.1 FPr TTGTCTCTGCCTTGGACTATCTACA SEQ ID NO: 40 Probe TCACGGTACACAATCTTTCCGGA SEQ ID NO: 41 RPr CCAGCATTAGATTCTCCAACTTGA SEQ ID NO: 42 AL137428 AL137428.1 FPr CAAGAAGAGGCTCTACCCTGG SEQ ID NO: 43 Probe ACTGGGAATTTCCAAGGCCACCTT SEQ ID NO: 44 RPr AAATGAGCTCTGCGATCCTC SEQ ID NO: 45 ALCAM NM_001627.1 FPr GAGGAATATGGAATCCAAGGG SEQ ID NO: 46 Probe CCAGTTCCTGCCGTCTGCTCTTCT SEQ ID NO: 47 RPr GTGGCGGAGATCAAGAGG SEQ ID NO: 48 ALDH1A1 NM_000689.1 FPr GAAGGAGATAAGGAGGATGTTGACA SEQ ID NO: 49 Probe AGTGAAGGCCGCAAGACAGGCTTTTC SEQ ID NO: 50 RPr CGCCACGGAGATCCAATC SEQ ID NO: 51 ALDOA NM_000034.2 FPr GCCTGTACGTGCCAGCTC SEQ ID NO: 52 Probe TGCCAGAGCCTCAACTGTCTCTGC SEQ ID NO: 53 RPr TCATCGGAGCTTGATCTCG SEQ ID NO: 54 AMFR NM_001144.2 FPr GATGGTTCAGCTCTGCAAGGA SEQ ID NO: 55 Probe CGATTTGAATATCTTTCCTTCTCGCCCACC SEQ ID NO: 56 RPr TCGACCGTGGCTGCTCAT SEQ ID NO: 57 ANGPT2 NM_001147.1 FPr CCGTGAAAGCTGCTCTGTAA SEQ ID NO: 58 Probe AAGCTGACACAGCCCTCCCAAGTG SEQ ID NO: 59 RPr TTGCAGTGGGAAGAACAGTC SEQ ID NO: 60 ANTXR1 NM_032208.1 FPr CTCCAGGTGTACCTCCAACC SEQ ID NO: 61 Probe AGCCTTCTCCCACAGCTGCCTACA SEQ ID NO: 62 RPr GAGAAGGCTGGGAGACTCTG SEQ ID NO: 63 ANXA1 NM_000700.1 FPr GCCCCTATCCTACCTTCAATCC SEQ ID NO: 64 Probe TCCTCGGATGTCGCTGCCT SEQ ID NO: 65 RPr CCTTTAACCATTATGGCCTTATGC SEQ ID NO: 66 ANXA2 NM_004039.1 FPr CAAGACACTAAGGGCGACTACCA SEQ ID NO: 67 Probe CCACCACACAGGTACAGCAGCGCT SEQ ID NO: 68 RPr CGTGTCGGGCTTCAGTCAT SEQ ID NO: 69 ANXA5 NM_001154.2 FPr GCTCAAGCCTGGAAGATGAC SEQ ID NO: 70 Probe AGTACCCTGAAGTGTCCCCCACCA SEQ ID NO: 71 RPr AGAACCACCAACATCCGCT SEQ ID NO: 72 AP-1 (JUN NM_002228.2 FPr GACTGCAAAGATGGAAACGA SEQ ID NO: 73 official) Probe CTATGACGATGCCCTCAACGCCTC SEQ ID NO: 74 RPr TAGCCATAAGGTCCGCTCTC SEQ ID NO: 75 APC NM_000038.1 FPr GGACAGCAGGAATGTGTTTC SEQ ID NO: 76 Probe CATTGGCTCCCCGTGACCTGTA SEQ ID NO: 77 RPr ACCCACTCGATTTGTTTCTG SEQ ID NO: 78 APEX-1 NM_001641.2 FPr GATGAAGCCTTTCGCAAGTT SEQ ID NO: 79 Probe CTTTCGGGAAGCCAGGCCCTT SEQ ID NO: 80 RPr AGGTCTCCACACAGCACAAG SEQ ID NO: 81 APG-1 NM_014278.2 FPr ACCCCGGCCTGTATATCAT SEQ ID NO: 82 Probe CCAATGGCTCGAGTTCTTGATCCC SEQ ID NO: 83 RPr CTATCTGGCTCTTTGCTGCAT SEQ ID NO: 84 APN NM_001150.1 FPr CCACCTTGGACCAAAGTAAAGC SEQ ID NO: 85 (ANPEP official) Probe CTCCCCAACACGCTGAAACCCG SEQ ID NO: 86 RPr TCTCAGCGTCACCTGGTAGGA SEQ ID NO: 87 APOC1 NM_001645.3 FPr GGAAACACACTGGAGGACAAG SEQ ID NO: 88 Probe TCATCAGCCGCATCAAACAGAGTG SEQ ID NO: 89 RPr CGCATCTTGGCAGAAAGTT SEQ ID NO: 90 AREG NM_001657.1 FPr TGTGAGTGAAATGCCTTCTAGTAGTGA SEQ ID NO: 91 Probe CCGTCCTCGGGAGCCGACTATGA SEQ ID NO: 92 RPr TTGTGGTTCGTTATCATACTCTTCTGA SEQ ID NO: 93 ARG NM_005158.2 FPr CGCAGTGCAGCTGAGTATCTG SEQ ID NO: 94 Probe TCGCACCAGGAAGCTGCCATTGA SEQ ID NO: 95 RPr TGCCCAGGGCTACTCTCACTT SEQ ID NO: 96 ARHF NM_019034.2 FPr ACTGGCCCACTTAGTCCTCA SEQ ID NO: 97 Probe CTCCCAACCTGCTGTCCCTCAAG SEQ ID NO: 98 RPr CTGAACTCCACAGGCTGGTA SEQ ID NO: 99 ATOH1 NM_005172.1 FPr GCAGCCACCTGCAACTTT SEQ ID NO: 100 Probe CAGGCGAGAGAGCATCCCGTCTAC SEQ ID NO: 101 RPr TCCAGGAGGGACAGCTCA SEQ ID NO: 102 ATP5A1 NM_004046.3 FPr GATGCTGCCACTCAACAACT SEQ ID NO: 103 Probe AGTTAGACGCACGCCACGACTCAA SEQ ID NO: 104 RPr TGTCCTTGCTTCAGCAACTC SEQ ID NO: 105 ATP5E NM_006886.2 FPr CCGCTTTCGCTACAGCAT SEQ ID NO: 106 Probe TCCAGCCTGTCTCCAGTAGGCCAC SEQ ID NO: 107 RPr TGGGAGTATCGGATGTAGCTG SEQ ID NO: 108 AURKB NM_004217.1 FPr AGCTGCAGAAGAGCTGCACAT SEQ ID NO: 109 Probe TGACGAGCAGCGAACAGCCACG SEQ ID NO: 110 RPr GCATCTGCCAACTCCTCCAT SEQ ID NO: 111 Axin 2 NM_004655.2 FPr GGCTATGTCTTTGCACCAGC SEQ ID NO: 112 Probe ACCAGCGCCAACGACAGTGAGATA SEQ ID NO: 113 RPr ATCCGTCAGCGCATCACT SEQ ID NO: 114 axin1 NM_003502.2 FPr CCGTGTGACAGCATCGTT SEQ ID NO: 115 Probe CGTACTACTTCTGCGGGGAACCCA SEQ ID NO: 116 RPr CTCACCAGGGTGCGGTAG SEQ ID NO: 117 B-Catenin NM_001904.1 FPr GGCTCTTGTGCGTACTGTCCTT SEQ ID NO: 118 Probe AGGCTCAGTGATGTCTTCCCTGTCACCAG SEQ ID NO: 119 RPr TCAGATGACGAAGAGCACAGATG SEQ ID NO: 120 BAD NM_032989.1 FPr GGGTCAGGTGCCTCGAGAT SEQ ID NO: 121 Probe TGGGCCCAGAGCATGTTCCAGATC SEQ ID NO: 122 RPr CTGCTCACTCGGCTCAAACTC SEQ ID NO: 123 BAG1 NM_004323.2 FPr CGTTGTCAGCACTTGGAATACAA SEQ ID NO: 124 Probe CCCAATTAACATGACCCGGCAACCAT SEQ ID NO: 125 RPr GTTCAACCTCTTCCTGTGGACTGT SEQ ID NO: 126 BAG2 NM_004282.2 FPr CTAGGGGCAAAAAGCATGA SEQ ID NO: 127 Probe TTCCATGCCAGACAGGAAAAAGCA SEQ ID NO: 128 RPr CTAAATGCCCAAGGTGACTG SEQ ID NO: 129 BAG3 NM_004281.2 FPr GAAAGTAAGCCAGGCCCAGTT SEQ ID NO: 130 Probe CAGAACTCCCTCCTGGACACATCCCAA SEQ ID NO: 131 RPr ACCTCTTTGCGGATCACTTGA SEQ ID NO: 132 Bak NM_001188.1 FPr CCATTCCCACCATTCTACCT SEQ ID NO: 133 Probe ACACCCCAGACGTCCTGGCCT SEQ ID NO: 134 RPr GGGAACATAGACCCACCAAT SEQ ID NO: 135 Bax NM_004324.1 FPr CCGCCGTGGACACAGACT SEQ ID NO: 136 Probe TGCCACTCGGAAAAAGACCTCTCGG SEQ ID NO: 137 RPr TTGCCGTCAGAAAACATGTCA SEQ ID NO: 138 BBC3 NM_014417.1 FPr CCTGGAGGGTCCTGTACAAT SEQ ID NO: 139 Probe CATCATGGGACTCCTGCCCTTACC SEQ ID NO: 140 RPr CTAATTGGGCTCCATCTCG SEQ ID NO: 141 BCAS1 NM_003657.1 FPr CCCCGAGACAACGGAGATAA SEQ ID NO: 142 Probe CTTTCCGTTGGCATCCGCAACAG SEQ ID NO: 143 RPr CTCGGGTTTGGCCTCTTTC SEQ ID NO: 144 Bcl2 NM_000633.1 FPr CAGATGGACCTAGTACCCACTGAGA SEQ ID NO: 145 Probe TTCCACGCCGAAGGACAGCGAT SEQ ID NO: 146 RPr CCTATGATTTAAGGGCATTTTTCC SEQ ID NO: 147 BCL2L10 NM_020396.2 FPr GCTGGGATGGCTTTTGTCA SEQ ID NO: 148 Probe TCTTCAGGACCCCCTTTCCACTGGC SEQ ID NO: 149 RPr GCCTGGACCAGCTGTTTTCTC SEQ ID NO: 150 BCL2L11 NM_138621.1 FPr AATTACCAAGCAGCCGAAGA SEQ ID NO: 151 Probe CCACCCACGAATGGTTATCTTACGACTG SEQ ID NO: 152 RPr CAGGCGGACAATGTAACGTA SEQ ID NO: 153 BCL2L12 NM_138639.1 FPr AACCCACCCCTGTCTTGG SEQ ID NO: 154 Probe TCCGGGTAGCTCTCAAACTCGAGG SEQ ID NO: 155 RPr CTCAGCTGACGGGAAAGG SEQ ID NO: 156 Bclx NM_001191.1 FPr CTTTTGTGGAACTCTATGGGAACA SEQ ID NO: 157 Probe TTCGGCTCTCGGCTGCTGCA SEQ ID NO: 158 RPr CAGCGGTTGAAGCGTTCCT SEQ ID NO: 159 BCRP NM_004827.1 FPr TGTACTGGCGAAGAATATTTGGTAAA SEQ ID NO: 160 Probe CAGGGCATCGATCTCTCACCCTGG SEQ ID NO: 161 RPr GCCACGTGATTCTTCCACAA SEQ ID NO: 162 BFGF NM_007083.1 FPr CCAGGAAGAATGCTTAAGATGTGA SEQ ID NO: 163 Probe TTCGCCAGGTCATTGAGATCCATCCA SEQ ID NO: 164 RPr TGGTGATGGGAGTTGTATTTTCAG SEQ ID NO: 165 BGN NM_001711.3 FPr GAGCTCCGCAAGGATGAC SEQ ID NO: 166 Probe CAAGGGTCTCCAGCACCTCTACGC SEQ ID NO: 167 RPr CTTGTTGTTCACCAGGACGA SEQ ID NO: 168 BID NM_001196.2 FPr GGACTGTGAGGTCAACAACG SEQ ID NO: 169 Probe TGTGATGCACTCATCCCTGAGGCT SEQ ID NO: 170 RPr GGAAGCCAAACACCAGTAGG SEQ ID NO: 171 BIK NM_001197.3 FPr ATTCCTATGGCTCTGCAATTGTC SEQ ID NO: 172 Probe CCGGTTAACTGTGGCCTGTGCCC SEQ ID NO: 173 RPr GGCAGGAGTGAATGGCTCTTC SEQ ID NO: 174 BIN1 NM_004305.1 FPr CCTGCAAAAGGGAACAAGAG SEQ ID NO: 175 Probe CTTCGCCTCCAGATGGCTCCC SEQ ID NO: 176 RPr CGTGGTTGACTCTGATCTCG SEQ ID NO: 177 BLMH NM_000386.2 FPr GGTTGCTGCCTCCATCAAAG SEQ ID NO: 178 Probe ACATCACAGCCAAACCACACAGCCTCT SEQ ID NO: 179 RPr CCAGCTTGCTATTGAAGTGTTTTC SEQ ID NO: 180 BMP2 NM_001200.1 FPr ATGTGGACGCTCTTTCAATG SEQ ID NO: 181 Probe ACCGCAGTCCGTCTAAGAAGCACG SEQ ID NO: 182 RPr ACCATGGTCGACCTTTAGGA SEQ ID NO: 183 BMP4 NM_001202.2 FPr GGGCTAGCCATTGAGGTG SEQ ID NO: 184 Probe CTCACCTCCATCAGACTCGGACCC SEQ ID NO: 185 RPr GCTAATCCTGACATGCTGGC SEQ ID NO: 186 BMP7 NM_001719.1 FPr TCGTGGAACATGACAAGGAATT SEQ ID NO: 187 Probe TTCCACCCACGCTACCACCATCG SEQ ID NO: 188 RPr TGGAAAGATCAAACCGGAACTC SEQ ID NO: 189 BMPR1A NM_004329.2 FPr TTGGTTCAGCGAACTATTGC SEQ ID NO: 190 Probe CAAACAGATTCAGATGGTCCGGCA SEQ ID NO: 191 RPr TCTCCATATCGGCCTTTACC SEQ ID NO: 192 BRAF NM_004333.1 FPr CCTTCCGACCAGCAGATGAA SEQ ID NO: 193 Probe CAATTTGGGCAACGAGACCGATCCT SEQ ID NO: 194 RPr TTTATATGCACATTGGGAGCTGAT SEQ ID NO: 195 BRCA1 NM_007295.1 FPr TCAGGGGGCTAGAAATCTGT SEQ ID NO: 196 Probe CTATGGGCCCTTCACCAACATGC SEQ ID NO: 197 RPr CCATTCCAGTTGATCTGTGG SEQ ID NO: 198 BRCA2 NM_000059.1 FPr AGTTCGTGCTTTGCAAGATG SEQ ID NO: 199 Probe CATTCTTCACTGCTTCATAAAGCTCTGCA SEQ ID NO: 200 RPr AAGGTAAGCTGGGTCTGCTG SEQ ID NO: 201 BRK NM_005975.1 FPr GTGCAGGAAAGGTTCACAAA SEQ ID NO: 202 Probe AGTGTCTGCGTCCAATACACGCGT SEQ ID NO: 203 RPr GCACACACGATGGAGTAAGG SEQ ID NO: 204 BTF3 NM_001207.2 FPr CAGTGATCCACTTTAACAACCCTAAAG SEQ ID NO: 205 Probe TCAGGCATCTCTGGCAGCGAACAC SEQ ID NO: 206 RPr AGCATGGCCTGTAATGGTGAA SEQ ID NO: 207 BTRC NM_033637.2 FPr GTTGGGACACAGTTGGTCTG SEQ ID NO: 208 Probe CAGTCGGCCCAGGACGGTCTACT SEQ ID NO: 209 RPr TGAAGCAGTCAGTTGTGCTG SEQ ID NO: 210 BUB1 NM_004336.1 FPr CCGAGGTTAATCCAGCACGTA SEQ ID NO: 211 Probe TGCTGGGAGCCTACACTTGGCCC SEQ ID NO: 212 RPr AAGACATGGCGCTCTCAGTTC SEQ ID NO: 213 BUB1B NM_001211.3 FPr TCAACAGAAGGCTGAACCACTAGA SEQ ID NO: 214 Probe TACAGTCCCAGCACCGACAATTCC SEQ ID NO: 215 RPr CAACAGAGTTTGCCGAGACACT SEQ ID NO: 216 BUB3 NM_004725.1 FPr CTGAAGCAGATGGTTCATCATT SEQ ID NO: 217 Probe CCTCGCTTTGTTTAACAGCCCAGG SEQ ID NO: 218 RPr GCTGATTCCCAAGAGTCTAACC SEQ ID NO: 219 c-abl NM_005157.2 FPr CCATCTCGCTGAGATACGAA SEQ ID NO: 220 Probe GGGAGGGTGTACCATTACAGGATCAACA SEQ ID NO: 221 RPr AGACGTAGAGCTTGCCATCA SEQ ID NO: 222 c-kit NM_000222.1 FPr GAGGCAACTGCTTATGGCTTAATTA SEQ ID NO: 223 Probe TTACAGCGACAGTCATGGCCGCAT SEQ ID NO: 224 RPr GGCACTCGGCTTGAGCAT SEQ ID NO: 225 c-myb NM_005375.1 FPr AACTCAGACTTGGAAATGCCTTCT SEQ ID NO: 226 (MYB official) Probe AACTTCCACCCCCCTCATTGGTCACA SEQ ID NO: 227 RPr CTGGTCTCTATGAAATGGTGTTGTAAC SEQ ID NO: 228 c-Src NM_005417.3 FPr TGAGGAGTGGTATTTTGGCAAGA SEQ ID NO: 229 Probe AACCGCTCTGACTCCCGTCTGGTG SEQ ID NO: 230 RPr CTCTCGGGTTCTCTGCATTGA SEQ ID NO: 231 C20 orf1 NM_012112.2 FPr TCAGCTGTGAGCTGCGGATA SEQ ID NO: 232 Probe CAGGTCCCATTGCCGGGCG SEQ ID NO: 233 RPr ACGGTCCTAGGTTTGAGGTTAAGA SEQ ID NO: 234 C20ORF126 NM_030815.2 FPr CCAGCACTGCTCGTTACTGT SEQ ID NO: 235 Probe TGGGACCTCAGACCACTGAAGGC SEQ ID NO: 236 RPr TTGACTTCACGGCAGTTCATA SEQ ID NO: 237 C8orf4 NM_020130.2 FPr CTACGAGTCAGCCCATCCAT SEQ ID NO: 238 Probe CATGGCTACCACTTCGACACAGCC SEQ ID NO: 239 RPr TGCCCACGGCTTTCTTAC SEQ ID NO: 240 CA9 NM_001216.1 FPr ATCCTAGCCCTGGTTTTTGG SEQ ID NO: 241 Probe TTTGCTGTCACCAGCGTCGC SEQ ID NO: 242 RPr CTGCCTTCTCATCTGCACAA SEQ ID NO: 243 Cad17 NM_004063.2 FPr GAAGGCCAAGAACCGAGTCA SEQ ID NO: 244 Probe TTATATTCCAGTTTAAGGCCAATCCTC SEQ ID NO: 245 RPr TCCCCAGTTAGTTCAAAAGTCACA SEQ ID NO: 246 CALD1 NM_004342.4 FPr CACTAAGGTTTGAGACAGTTCCAGAA SEQ ID NO: 247 Probe AACCCAAGCTCAAGACGCAGGACGAG SEQ ID NO: 248 RPr GCGAATTAGCCCTCTACAACTGA SEQ ID NO: 249 CAPG NM_001747.1 FPr GATTGTCACTGATGGGGAGG SEQ ID NO: 250 Probe AGGACCTGGATCATCTCAGCAGGC SEQ ID NO: 251 RPr CCTTCAGAGCAGGCTTGG SEQ ID NO: 252 CAPN1 NM_005186.2 FPr CAAGAAGCTGTACGAGCTCATCA SEQ ID NO: 253 Probe CCGCTACTCGGAGCCCGACCTG SEQ ID NO: 254 RPr GCAGCAAACGAAATTGTCAAAG SEQ ID NO: 255 CASP8 NM_033357.1 FPr CCTCGGGGATACTGTCTGAT SEQ ID NO: 256 Probe CAACAATCACAATTTTGCAAAAGCACG SEQ ID NO: 257 RPr GAAGTTTGGGCACTTTCTCC SEQ ID NO: 258 CASP9 NM_001229.2 FPr TGAATGCCGTGGATTGCA SEQ ID NO: 259 Probe CACTAGCCCTGGACCAGCCACTGCT SEQ ID NO: 260 RPr ACAGGGATCATGGGACACAAG SEQ ID NO: 261 CAT NM_001752.1 FPr ATCCATTCGATCTCACCAAGGT SEQ ID NO: 262 Probe TGGCCTCACAAGGACTACCCTCTCATCC SEQ ID NO: 263 RPr TCCGGTTTAAGACCAGTTTACCA SEQ ID NO: 264 CAV1 NM_001753.3 FPr GTGGCTCAACATTGTGTTCC SEQ ID NO: 265 Probe ATTTCAGCTGATCAGTGGGCCTCC SEQ ID NO: 266 RPr CAATGGCCTCCATTTTACAG SEQ ID NO: 267 CBL NM_005188.1 FPr TCATTCACAAACCTGGCAGT SEQ ID NO: 268 Probe TTCCGGCTGAGCTGTACTCGTCTG SEQ ID NO: 269 RPr CATACCCAATAGCCCACTGA SEQ ID NO: 270 CCL20 NM_004591.1 FPr CCATGTGCTGTACCAAGAGTTTG SEQ ID NO: 271 Probe CAGCACTGACATCAAAGCAGCCAGGA SEQ ID NO: 272 RPr CGCCGCAGAGGTGGAGTA SEQ ID NO: 273 CCL3 NM_002983.1 FPr AGCAGACAGTGGTCAGTCCTT SEQ ID NO: 274 Probe CTCTGCTGACACTCGAGCCCACAT SEQ ID NO: 275 RPr CTGCATGATTCTGAGCAGGT SEQ ID NO: 276 CCNA2 NM_001237.2 FPr CCATACCTCAAGTATTTGCCATCAG SEQ ID NO: 277 Probe ATTGCTGGAGCTGCCTTTCATTTAGCACT SEQ ID NO: 278 RPr AGCTTTGTCCCGTGACTGTGTA SEQ ID NO: 279 CCNB1 NM_031966.1 FPr TTCAGGTTGTTGCAGGAGAC SEQ ID NO: 280 Probe TGTCTCCATTATTGATCGGTTCATGCA SEQ ID NO: 281 RPr CATCTTCTTGGGCACACAAT SEQ ID NO: 282 CCNB2 NM_004701.2 FPr AGGCTTCTGCAGGAGACTCTGT SEQ ID NO: 283 Probe TCGATCCATAATGCCAACGCACATG SEQ ID NO: 284 RPr GGGAAACTGGCTGAACCTGTAA SEQ ID NO: 285 CCND1 NM_001758.1 FPr GCATGTTCGTGGCCTCTAAGA SEQ ID NO: 286 Probe AAGGAGACCATCCCCCTGACGGC SEQ ID NO: 287 RPr CGGTGTAGATGCACAGCTTCTC SEQ ID NO: 288 CCND3 NM_001760.2 FPr CCTCTGTGCTACAGATTATACCTTTGC SEQ ID NO: 289 Probe TACCCGCCATCCATGATCGCCA SEQ ID NO: 290 RPr CACTGCAGCCCCAATGCT SEQ ID NO: 291 CCNE1 NM_001238.1 FPr AAAGAAGATGATGACCGGGTTTAC SEQ ID NO: 292 Probe CAAACTCAACGTGCAAGCCTCGGA SEQ ID NO: 293 RPr GAGCCTCTGGATGGTGCAAT SEQ ID NO: 294 CCNE2 NM_057749.1 FPr GGTCACCAAGAAACATCAGTATGAA SEQ ID NO: 295 Probe CCCAGATAATACAGGTGGCCAACAATTC SEQ ID NO: 296 CT RPr TTCAATGATAATGCAAGGACTGATC SEQ ID NO: 297 CCNE2 NM_057749var1 FPr ATGCTGTGGCTCCTTCCTAACT SEQ ID NO: 298 variant 1 Probe TACCAAGCAACCTACATGTCAAGAAAGC SEQ ID NO: 299 CC RPr ACCCAAATTGTGATATACAAAAAGGTT SEQ ID NO: 300 CCR7 NM_001838.2 FPr GGATGACATGCACTCAGCTC SEQ ID NO: 301 Probe CTCCCATCCCAGTGGAGCCAA SEQ ID NO: 302 RPr CCTGACATTTCCCTTGTCCT SEQ ID NO: 303 CD105 NM_000118.1 FPr GCAGGTGTCAGCAAGTATGATCAG SEQ ID NO: 304 Probe CGACAGGATATTGACCACCGCCTCATT SEQ ID NO: 305 RPr TTTTTCCGCTGTGGTGATGA SEQ ID NO: 306 CD134 NM_003327.1 FPr GCCCAGTGCGGAGAACAG SEQ ID NO: 307 (TNFRSF4 official) Probe CCAGCTTGATTCTCGTCTCTGCACTTAAGC SEQ ID NO: 308 RPr AATCACACGCACCTGGAGAAC SEQ ID NO: 309 CD18 NM_000211.1 FPr CGTCAGGACCCACCATGTCT SEQ ID NO: 310 Probe CGCGGCCGAGACATGGCTTG SEQ ID NO: 311 RPr GGTTAATTGGTGACATCCTCAAGA SEQ ID NO: 312 CD24 NM_013230.1 FPr TCCAACTAATGCCACCACCAA SEQ ID NO: 313 Probe CTGTTGACTGCAGGGCACCACCA SEQ ID NO: 314 RPr GAGAGAGTGAGACCACGAAGAGACT SEQ ID NO: 315 CD28 NM_006139.1 FPr TGTGAAAGGGAAACACCTTTG SEQ ID NO: 316 Probe CCAAGTCCCCTATTTCCCGGACCT SEQ ID NO: 317 RPr AGCACCCAAAAGGGCTTAG SEQ ID NO: 318 CD31 NM_000442.1 FPr TGTATTTCAAGACCTCTGTGCACTT SEQ ID NO: 319 Probe TTTATGAACCTGCCCTGCTCCCACA SEQ ID NO: 320 RPr TTAGCCTGAGGAATTGCTGTGTT SEQ ID NO: 321 CD34 NM_001773.1 FPr CCACTGCACACACCTCAGA SEQ ID NO: 322 Probe CTGTTCTTGGGGCCCTACACCTTG SEQ ID NO: 323 RPr CAGGAGTTTACCTGCCCCT SEQ ID NO: 324 CD3z NM_000734.1 FPr AGATGAAGTGGAAGGCGCTT SEQ ID NO: 325 Probe CACCGCGGCCATCCTGCA SEQ ID NO: 326 RPr TGCCTCTGTAATCGGCAACTG SEQ ID NO: 327 CD44E X55150 FPr ATCACCGACAGCACAGACA SEQ ID NO: 328 Probe CCCTGCTACCAATATGGACTCCAGTCA SEQ ID NO: 329 RPr ACCTGTGTTTGGATTTGCAG SEQ ID NO: 330 CD44s M59040.1 FPr GACGAAGACAGTCCCTGGAT SEQ ID NO: 331 Probe CACCGACAGCACAGACAGAATCCC SEQ ID NO: 332 RPr ACTGGGGTGGAATGTGTCTT SEQ ID NO: 333 CD44v3 AJ251595v3 FPr CACACAAAACAGAACCAGGACT SEQ ID NO: 334 Probe ACCCAGTGGAACCCAAGCCATTC SEQ ID NO: 335 RPr CTGAAGTAGCACTTCCGGATT SEQ ID NO: 336 CD44v6 AJ251595v6 FPr CTCATACCAGCCATCCAATG SEQ ID NO: 337 Probe CACCAAGCCCAGAGGACAGTTCCT SEQ ID NO: 338 RPr TTGGGTTGAAGAAATCAGTCC SEQ ID NO: 339 CD68 NM_001251.1 FPr TGGTTCCCAGCCCTGTGT SEQ ID NO: 340 Probe CTCCAAGCCCAGATTCAGATTCGAGTCA SEQ ID NO: 341 RPr CTCCTCCACCCTGGGTTGT SEQ ID NO: 342 CD80 NM_005191.2 FPr TTCAGTTGCTTTGCAGGAAG SEQ ID NO: 343 Probe TTCTGTGCCCACCATATTCCTCTAGACA SEQ ID NO: 344 RPr TTGATCAAGGTCACCAGAGC SEQ ID NO: 345 CD82 NM_002231.2 FPr GTGCAGGCTCAGGTGAAGTG SEQ ID NO: 346 Probe TCAGCTTCTACAACTGGACAGACAACGC SEQ ID NO: 347 TG RPr GACCTCAGGGCGATTCATGA SEQ ID NO: 348 CD8A NM_171827.1 FPr AGGGTGAGGTGCTTGAGTCT SEQ ID NO: 349 Probe CCAACGGCAAGGGAACAAGTACTTCT SEQ ID NO: 350 RPr GGGCACAGTATCCCAGGTA SEQ ID NO: 351 CD9 NM_001769.1 FPr GGGCGTGGAACAGTTTATCT SEQ ID NO: 352 Probe AGACATCTGCCCCAAGAAGGACGT SEQ ID NO: 353 RPr CACGGTGAAGGTTTCGAGT SEQ ID NO: 354 CDC2 NM_001786.2 FPr GAGAGCGACGCGGTTGTT SEQ ID NO: 355 Probe TAGCTGCCGCTGCGGCCG SEQ ID NO: 356 RPr GTATGGTAGATCCCGGCTTATTATTC SEQ ID NO: 357 CDC20 NM_001255.1 FPr TGGATTGGAGTTCTGGGAATG SEQ ID NO: 358 Probe ACTGGCCGTGGCACTGGACAACA SEQ ID NO: 359 RPr GCTTGCACTCCACAGGTACACA SEQ ID NO: 360 cdc25A NM_001789.1 FPr TCTTGCTGGCTACGCCTCTT SEQ ID NO: 361 Probe TGTCCCTGTTAGACGTCCTCCGTCCATA SEQ ID NO: 362 RPr CTGCATTGTGGCACAGTTCTG SEQ ID NO: 363 CDC25B NM_021874.1 FPr AAACGAGCAGTTTGCCATCAG SEQ ID NO: 364 Probe CCTCACCGGCATAGACTGGAAGCG SEQ ID NO: 365 RPr GTTGGTGATGTTCCGAAGCA SEQ ID NO: 366 CDC25C NM_001790.2 FPr GGTGAGCAGAAGTGGCCTAT SEQ ID NO: 367 Probe CTCCCCGTCGATGCCAGAGAACT SEQ ID NO: 368 RPr CTTCAGTCTTGGCCTGTTCA SEQ ID NO: 369 CDC4 NM_018315.2 FPr GCAGTCCGCTGTGTTCAA SEQ ID NO: 370 Probe TGCTCCACTAACAACCCTCCTGCC SEQ ID NO: 371 RPr GGATCCCACACCTTTACCATAA SEQ ID NO: 372 CDC42 NM_001791.2 FPr TCCAGAGACTGCTGAAAA SEQ ID NO: 373 Probe CCCGTGACCTGAAGGCTGTCAAG SEQ ID NO: 374 RPr TGTGTAAGTGCAGAACAC SEQ ID NO: 375 CDC42BPA NM_003607.2 FPr GAGCTGAAAGACGCACACTG SEQ ID NO: 376 Probe AATTCCTGCATGGCCAGTTTCCTC SEQ ID NO: 377 RPr GCCGCTCATTGATCTCCA SEQ ID NO: 378 CDC6 NM_001254.2 FPr GCAACACTCCCCATTTACCTC SEQ ID NO: 379 Probe TTGTTCTCCACCAAAGCAAGGCAA SEQ ID NO: 380 RPr TGAGGGGGACCATTCTCTTT SEQ ID NO: 381 CDCA7 v2 NM_145810.1 FPr AAGACCGTGGATGGCTACAT SEQ ID NO: 382 Probe ATGAAGATGACCTGCCCAGAAGCC SEQ ID NO: 383 RPr AGGGTCACGGATGATCTGG SEQ ID NO: 384 CDH1 NM_004360.2 FPr TGAGTGTCCCCCGGTATCTTC SEQ ID NO: 385 Probe TGCCAATCCCGATGAAATTGGAAATTT SEQ ID NO: 386 RPr CAGCCGCTTTCAGATTTTCAT SEQ ID NO: 387 CDH11 NM_001797.2 FPr GTCGGCAGAAGCAGGACT SEQ ID NO: 388 Probe CCTTCTGCCCATAGTGATCAGCGA SEQ ID NO: 389 RPr CTACTCATGGGCGGGATG SEQ ID NO: 390 CDH3 NM_001793.3 FPr ACCCATGTACCGTCCTCG SEQ ID NO: 391 Probe CCAACCCAGATGAAATCGGCAACT SEQ ID NO: 392 RPr CCGCCTTCAGGTTCTCAAT SEQ ID NO: 393 CDK2 NM_001798.2 FPr AATGCTGCACTACGACCCTA SEQ ID NO: 394 Probe CCTTGGCCGAAATCCGCTTGT SEQ ID NO: 395 RPr TTGGTCACATCCTGGAAGAA SEQ ID NO: 396 CDX1 NM_001804.1 FPr AGCAACACCAGCCTCCTG SEQ ID NO: 397 Probe CACCTCCTCTCCAATGCCTGTGAA SEQ ID NO: 398 RPr GGGCTATGGCAGAAACTCCT SEQ ID NO: 399 Cdx2 NM_001265.2 FPr GGGCAGGCAAGGTTTACA SEQ ID NO: 400 Probe ATCTTAGCTGCCTTTGGCTTCCGC SEQ ID NO: 401 RPr GTCTTTGGTCAGTCCAGCTTTC SEQ ID NO: 402 CEACAM1 NM_001712.2 FPr ACTTGCCTGTTCAGAGCACTCA SEQ ID NO: 403 Probe TCCTTCCCACCCCCAGTCCTGTC SEQ ID NO: 404 RPr TGGCAAATCCGAATTAGAGTGA SEQ ID NO: 405 CEACAM6 NM_002483.2 FPr CACAGCCTCACTTCTAACCTTCTG SEQ ID NO: 406 Probe ACCCACCCACCACTGCCAAGCTC SEQ ID NO: 407 RPr TTGAATGGCGTGGATTCAATAG SEQ ID NO: 408 CEBPB NM_005194.2 FPr GCAACCCACGTGTAACTGTC SEQ ID NO: 409 Probe CCGGGCCCTGAGTAATCGCTTAA SEQ ID NO: 410 RPr ACAAGCCCGTAGGAACATCT SEQ ID NO: 411 CEGP1 NM_020974.1 FPr TGACAATCAGCACACCTGCAT SEQ ID NO: 412 Probe CAGGCCCTCTTCCGAGCGGT SEQ ID NO: 413 RPr TGTGACTACAGCCGTGATCCTTA SEQ ID NO: 414 CENPA NM_001809.2 FPr TAAATTCACTCGTGGTGTGGA SEQ ID NO: 415 Probe CTTCAATTGGCAAGCCCAGGC SEQ ID NO: 416 RPr GCCTCTTGTAGGGCCAATAG SEQ ID NO: 417 CENPE NM_001813.1 FPr GGATGCTGGTGACCTCTTCT SEQ ID NO: 418 Probe TCCCTCACGTTGCAACAGGAATTAA SEQ ID NO: 419 RPr GCCAAGGCACCAAGTAACTC SEQ ID NO: 420 CENPF NM_016343.2 FPr CTCCCGTCAACAGCGTTC SEQ ID NO: 421 Probe ACACTGGACCAGGAGTGCATCCAG SEQ ID NO: 422 RPr GGGTGAGTCTGGCCTTCA SEQ ID NO: 423 CES2 NM_003869.4 FPr ACTTTGCGAGAAATGGGAAC SEQ ID NO: 424 Probe AGTGTGGCAGACCCTCGCCATT SEQ ID NO: 425 RPr CAGGTATTGCTCCTCCTGGT SEQ ID NO: 426 CGA NM_001275.2 FPr CTGAAGGAGCTCCAAGACCT SEQ ID NO: 427 (CHGA official) Probe TGCTGATGTGCCCTCTCCTTGG SEQ ID NO: 428 RPr CAAAACCGCTGTGTTTCTTC SEQ ID NO: 429 CGB NM_000737.2 FPr CCACCATAGGCAGAGGCA SEQ ID NO: 430 Probe ACACCCTACTCCCTGTGCCTCCAG SEQ ID NO: 431 RPr AGTCGTCGAGTGCTAGGGAC SEQ ID NO: 432 CHAF1B NM_005441.1 FPr GAGGCCAGTGGTGGAAACAG SEQ ID NO: 433 Probe AGCTGATGAGTCTGCCCTACCGCCTG SEQ ID NO: 434 RPr TCCGAGGCCACAGCAAAC SEQ ID NO: 435 CHD2 NM_001271.1 FPr CTCTGTGCGAGGCTGTCA SEQ ID NO: 436 Probe ACCCATCTCGGGATCCCTGATACC SEQ ID NO: 437 RPr GGTAAGGACTGTGGGCTGG SEQ ID NO: 438 CHFR NM_018223.1 FPr AAGGAAGTGGTCCCTCTGTG SEQ ID NO: 439 Probe TGAAGTCTCCAGCTTTGCCTCAGC SEQ ID NO: 440 RPr GACGCAGTCTTTCTGTCTGG SEQ ID NO: 441 Chk1 NM_001274.1 FPr GATAAATTGGTACAAGGGATCAGCTT SEQ ID NO: 442 Probe CCAGCCCACATGTCCTGATCATATGC SEQ ID NO: 443 RPr GGGTGCCAAGTAACTGACTATTCA SEQ ID NO: 444 Chk2 NM_007194.1 FPr ATGTGGAACCCCCACCTACTT SEQ ID NO: 445 Probe AGTCCCAACAGAAACAAGAACTTCAGGCG SEQ ID NO: 446 RPr CAGTCCACAGCACGGTTATACC SEQ ID NO: 447 CIAP1 NM_001166.2 FPr TGCCTGTGGTGGGAAGCT SEQ ID NO: 448 Probe TGACATAGCATCATCCTTTGGTTCCCAGTT SEQ ID NO: 449 RPr GGAAAATGCCTCCGGTGTT SEQ ID NO: 450 cIAP2 NM_001165.2 FPr GGATATTTCCGTGGCTCTTATTCA SEQ ID NO: 451 Probe TCTCCATCAAATCCTGTAAACTCCAGAG SEQ ID NO: 452 CA RPr CTTCTCATCAAGGCAGAAAAATCTT SEQ ID NO: 453 CKS1B NM_001826.1 FPr GGTCCCTAAAACCCATCTGA SEQ ID NO: 454 Probe TGAACGCCAAGATTCCTCCATTCA SEQ ID NO: 455 RPr TAATGGACCCATCCCTGACT SEQ ID NO: 456 CKS2 NM_001827.1 FPr GGCTGGACGTGGTTTTGTCT SEQ ID NO: 457 Probe CTGCGCCCGCTCTTCGCG SEQ ID NO: 458 RPr CGCTGCAGAAAATGAAACGA SEQ ID NO: 459 Claudin 4 NM_001305.2 FPr GGCTGCTTTGCTGCAACTG SEQ ID NO: 460 Probe CGCACAGACAAGCCTTACTCCGCC SEQ ID NO: 461 RPr CAGAGCGGGCAGCAGAATA SEQ ID NO: 462 CLDN1 NM_021101.3 FPr TCTGGGAGGTGCCCTACTT SEQ ID NO: 463 Probe TGTTCCTGTCCCCGAAAAACAACC SEQ ID NO: 464 RPr TGGATAGGGCCTTGGTGTT SEQ ID NO: 465 CLDN7 NM_001307.3 FPr GGTCTGCCCTAGTCATCCTG SEQ ID NO: 466 Probe TGCACTGCTCTCCTGTTCCTGTCC SEQ ID NO: 467 RPr GTACCCAGCCTTGCTCTCAT SEQ ID NO: 468 CLIC1 NM_001288.3 FPr CGGTACTTGAGCAATGCCTA SEQ ID NO: 469 Probe CGGGAAGAATTCGCTTCCACCTG SEQ ID NO: 470 RPr TCGATCTCCTCATCATCTGG SEQ ID NO: 471 CLTC NM_004859.1 FPr ACCGTATGGACAGCCACAG SEQ ID NO: 472 Probe TCTCACATGCTGTACCCAAAGCCA SEQ ID NO: 473 RPr TGACTACAGGATCAGCGCTTC SEQ ID NO: 474 CLU NM_001831.1 FPr CCCCAGGATACCTACCACTACCT SEQ ID NO: 475 Probe CCCTTCAGCCTGCCCCACCG SEQ ID NO: 476 RPr TGCGGGACTTGGGAAAGA SEQ ID NO: 477 cMet NM_000245.1 FPr GACATTTCCAGTCCTGCAGTCA SEQ ID NO: 478 Probe TGCCTCTCTGCCCCACCCTTTGT SEQ ID NO: 479 RPr CTCCGATCGCACACATTTGT SEQ ID NO: 480 cMYC NM_002467.1 FPr TCCCTCCACTCGGAAGGACTA SEQ ID NO: 481 Probe TCTGACACTGTCCAACTTGACCCTCTT SEQ ID NO: 482 RPr CGGTTGTTGCTGATCTGTCTCA SEQ ID NO: 483 CNN NM_001299.2 FPr TCCACCCTCCTGGCTTTG SEQ ID NO: 484 Probe TCCTTTCGTCTTCGCCATGCTGG SEQ ID NO: 485 RPr TCACTCCCACGTTCACCTTGT SEQ ID NO: 486 COL1A1 NM_000088.2 FPr GTGGCCATCCAGCTGACC SEQ ID NO: 487 Probe TCCTGCGCCTGATGTCCACCG SEQ ID NO: 488 RPr CAGTGGTAGGTGATGTTCTGGGA SEQ ID NO: 489 COL1A2 NM_000089.2 FPr CAGCCAAGAACTGGTATAGGAGCT SEQ ID NO: 490 Probe TCTCCTAGCCAGACGTGTTTCTTGTCCTTG SEQ ID NO: 491 RPr AAACTGGCTGCCAGCATTG SEQ ID NO: 492 COPS3 NM_003653.2 FPr ATGCCCAGTGTTCCTGACTT SEQ ID NO: 493 Probe CGAAACGCTATTCTCACAGGTTCAGC SEQ ID NO: 494 RPr CTCCCCATTACAAGTGCTGA SEQ ID NO: 495 COX2 NM_000963.1 FPr TCTGCAGAGTTGGAAGCACTCTA SEQ ID NO: 496 Probe CAGGATACAGCTCCACAGCATCGATGTC SEQ ID NO: 497 RPr GCCGAGGCTTTTCTACCAGAA SEQ ID NO: 498 COX3 MITO_COX3 FPr TCGAGTCTCCCTTCACCATT SEQ ID NO: 499 Probe CGACGGCATCTACGGCTCAACAT SEQ ID NO: 500 RPr GACGTGAAGTCCGTGGAAG SEQ ID NO: 501 CP NM_000096.1 FPr CGTGAGTACACAGATGCCTCC SEQ ID NO: 502 Probe TCTTCAGGGCCTCTCTCCTTTCGA SEQ ID NO: 503 RPr CCAGGATGCCAAGATGCT SEQ ID NO: 504 CRBP NM_002899.2 FPr TGGTCTGCAAGCAAGTATTCAAG SEQ ID NO: 505 Probe TCTGCTTGGGCCTCACTGCACCT SEQ ID NO: 506 RPr GCTGATTGGTTGGGACAAGGT SEQ ID NO: 507 CREBBP NM_004380.1 FPr TGGGAAGCAGCTGTGTACCAT SEQ ID NO: 508 Probe CCTCGCGATGCTGCCTACTACAGCTATC SEQ ID NO: 509 RPr GAAACACTTCTCACAGAAATGATACCTA SEQ ID NO: 510 TT CRIP2 NM_001312.1 FPr GTGCTACGCCACCCTGTT SEQ ID NO: 511 Probe CCGATGTTCACGCCTTTGGGTC SEQ ID NO: 512 RPr CAGGGGCTTCTCGTAGATGT SEQ ID NO: 513 cripto NM_003212.1 FPr GGGTCTGTGCCCCATGAC SEQ ID NO: 514 (TDGF1 official) Probe CCTGGCTGCCCAAGAAGTGTTCCCT SEQ ID NO: 515 RPr TGACCGTGCCAGCATTTACA SEQ ID NO: 516 CRK(a) NM_016823.2 FPr CTCCCTAACCTCCAGAATGG SEQ ID NO: 517 Probe ACTCGCTTCTGGATAACCCTGGCA SEQ ID NO: 518 RPr TGTCTTGTCGTAGGCATTGG SEQ ID NO: 519 CRMP1 NM_001313.1 FPr AAGGTTTTTGGATTGCAAGG SEQ ID NO: 520 Probe ACCGTCATACATGCCCCTGGAAAC SEQ ID NO: 521 RPr GGGTGTAGCTGGTACCTCGT SEQ ID NO: 522 CRYAB NM_001885.1 FPr GATGTGATTGAGGTGCATGG SEQ ID NO: 523 Probe TGTTCATCCTGGCGCTCTTCATGT SEQ ID NO: 524 RPr GAACTCCCTGGAGATGAAACC SEQ ID NO: 525 CSEL1 NM_001316.2 FPr TTACGCAGCTCATGCTCTTG SEQ ID NO: 526 Probe ACGGCTCTTTACTATGCGAGGGCC SEQ ID NO: 527 RPr GCAGCTGTAAAGAGAGTGGCAT SEQ ID NO: 528 CSF1 NM_000757.3 FPr TGCAGCGGCTGATTGACA SEQ ID NO: 529 Probe TCAGATGGAGACCTCGTGCCAAATTACA SEQ ID NO: 530 RPr CAACTGTTCCTGGTCTACAAACTCA SEQ ID NO: 531 CSK (SRC) NM_004383.1 FPr CCTGAACATGAAGGAGCTGA SEQ ID NO: 532 Probe TCCCGATGGTCTGCAGCAGCT SEQ ID NO: 533 RPr CATCACGTCTCCGAACTCC SEQ ID NO: 534 CTAG1B NM_001327.1 FPr GCTCTCCATCAGCTCCTGTC SEQ ID NO: 535 Probe CCACATCAACAGGGAAAGCTGCTG SEQ ID NO: 536 RPr AACACGGGCAGAAAGCACT SEQ ID NO: 537 CTGF NM_001901.1 FPr GAGTTCAAGTGCCCTGACG SEQ ID NO: 538 Probe AACATCATGTTCTTCTTCATGACCTCGC SEQ ID NO: 539 RPr AGTTGTAATGGCAGGCACAG SEQ ID NO: 540 CTHRC1 NM_138455.2 FPr GCTCACTTCGGCTAAAATGC SEQ ID NO: 541 Probe ACCAACGCTGACAGCATGCATTTC SEQ ID NO: 542 RPr TCAGCTCCATTGAATGTGAAA SEQ ID NO: 543 CTLA4 NM_005214.2 FPr CACTGAGGTCCGGGTGACA SEQ ID NO: 544 Probe CACCTGGCTGTCAGCCTGCCG SEQ ID NO: 545 RPr GTAGGTTGCCGCACAGACTTC SEQ ID NO: 546 CTNNBIP1 NM_020248.2 FPr GTTTTCCAGGTCGGAGACG SEQ ID NO: 547 Probe CTTTGCAGCTACTGCCTCCGGTCT SEQ ID NO: 548 RPr AGCATCCAGGGTGTTCCA SEQ ID NO: 549 CTSB NM_001908.1 FPr GGCCGAGATCTACAAAAACG SEQ ID NO: 550 Probe CCCCGTGGAGGGAGCTTTCTC SEQ ID NO: 551 RPr GCAGGAAGTCCGAATACACA SEQ ID NO: 552 CTSD NM_001909.1 FPr GTACATGATCCCCTGTGAGAAGGT SEQ ID NO: 553 Probe ACCCTGCCCGCGATCACACTGA SEQ ID NO: 554 RPr GGGACAGCTTGTAGCCTTTGC SEQ ID NO: 555 CTSH NM_004390.1 FPr GCAAGTTCCAACCTGGAAAG SEQ ID NO: 556 Probe TGGCTACATCCTTGACAAAGCCGA SEQ ID NO: 557 RPr CATCGCTTCCTCGTCATAGA SEQ ID NO: 558 CTSL NM_001912.1 FPr GGGAGGCTTATCTCACTGAGTGA SEQ ID NO: 559 Probe TTGAGGCCCAGAGCAGTCTACCAGATTCT SEQ ID NO: 560 RPr CCATTGCAGCCTTCATTGC SEQ ID NO: 561 CTSL2 NM_001333.2 FPr TGTCTCACTGAGCGAGCAGAA SEQ ID NO: 562 Probe CTTGAGGACGCGAACAGTCCACCA SEQ ID NO: 563 RPr ACCATTGCAGCCCTGATTG SEQ ID NO: 564 CUL1 NM_003592.2 FPr ATGCCCTGGTAATGTCTGCAT SEQ ID NO: 565 Probe CAGCCACAAAGCCAGCGTCATTGT SEQ ID NO: 566 RPr GCGACCACAAGCCTTATCAAG SEQ ID NO: 567 CUL4A NM_003589.1 FPr AAGCATCTTCCTGTTCTTGGA SEQ ID NO: 568 Probe TATGTGCTGCAGAACTCCACGCTG SEQ ID NO: 569 RPr AATCCCATATCCCAGATGGA SEQ ID NO: 570 CXCL12 NM_000609.3 FPr GAGCTACAGATGCCCATGC SEQ ID NO: 571 Probe TTCTTCGAAAGCCATGTTGCCAGA SEQ ID NO: 572 RPr TTTGAGATGCTTGACGTTGG SEQ ID NO: 573 CXCR4 NM_003467.1 FPr TGACCGCTTCTACCCCAATG SEQ ID NO: 574 Probe CTGAAACTGGAACACAACCACCCACAAG SEQ ID NO: 575 RPr AGGATAAGGCCAACCATGATGT SEQ ID NO: 576 CYBA NM_000101.1 FPr GGTGCCTACTCCATTGTGG SEQ ID NO: 577 Probe TACTCCAGCAGGCACACAAACACG SEQ ID NO: 578 RPr GTGGAGCCCTTCTTCCTCTT SEQ ID NO: 579 CYP1B1 NM_000104.2 FPr CCAGCTTTGTGCCTGTCACTAT SEQ ID NO: 580 Probe CTCATGCCACCACTGCCAACACCTC SEQ ID NO: 581 RPr GGGAATGTGGTAGCCCAAGA SEQ ID NO: 582 CYP2C8 NM_000770.2 FPr CCGTGTTCAAGAGGAAGCTC SEQ ID NO: 583 Probe TTTTCTCAACTCCTCCACAAGGCA SEQ ID NO: 584 RPr AGTGGGATCACAGGGTGAAG SEQ ID NO: 585 CYP3A4 NM_017460.3 FPr AGAACAAGGACAACATAGATCCTTACAT SEQ ID NO: 586 AT Probe CACACCCTTTGGAAGTGGACCCAGAA SEQ ID NO: 587 RPr GCAAACCTCATGCCAATGC SEQ ID NO: 588 CYR61 NM_001554.3 FPr TGCTCATTCTTGAGGAGCAT SEQ ID NO: 589 Probe CAGCACCCTTGGCAGTTTCGAAAT SEQ ID NO: 590 RPr GTGGCTGCATTAGTGTCCAT SEQ ID NO: 591 DAPK1 NM_004938.1 FPr CGCTGACATCATGAATGTTCCT SEQ ID NO: 592 Probe TCATATCCAAACTCGCCTCCAGCCG SEQ ID NO: 593 RPr TCTCTTTCAGCAACGATGTGTCTT SEQ ID NO: 594 DCC NM_005215.1 FPr AAATGTCCTCCTCGACTGCT SEQ ID NO: 595 Probe ATCACTGGAACTCCTCGGTCGGAC SEQ ID NO: 596 RPr TGAATGCCATCTTTCTTCCA SEQ ID NO: 597 DCC_exons X76132_18-23 FPr GGTCACCGTTGGTGTCATCA SEQ ID NO: 598 18-23 Probe CAGCCACGATGACCACTACCAGCACT SEQ ID NO: 599 RPr GAGCGTCGGGTGCAAATC SEQ ID NO: 600 DCC_exons X76132_6-7 FPr ATGGAGATGTGGTCATTCCTAGTG SEQ ID NO: 601 6-7 Probe TGCTTCCTCCCACTATCTGAAAATAA SEQ ID NO: 602 RPr CACCACCCCAAGTATCCGTAAG SEQ ID NO: 603 DCK NM_000788.1 FPr GCCGCCACAAGACTAAGGAAT SEQ ID NO: 604 Probe AGCTGCCCGTCTTTCTCAGCCAGC SEQ ID NO: 605 RPr CGATGTTCCCTTCGATGGAG SEQ ID NO: 606 DDB1 NM_001923.2 FPr TGCGGATCATCCGGAATG SEQ ID NO: 607 Probe AATTGGAATCCACGAGCATGCCAGC SEQ ID NO: 608 RPr TCCTTTGATGCCTGGTAAGTCA SEQ ID NO: 609 DET1 NM_017996.2 FPr CTTGTGGAGATCACCCAATCAG SEQ ID NO: 610 Probe CTATGCCCGGGACTCGGGCCT SEQ ID NO: 611 RPr CCCGCCTGGATCTCAAACT SEQ ID NO: 612 DHFR NM_000791.2 FPr TTGCTATAACTAAGTGCTTCTCCAAGA SEQ ID NO: 613 Probe CCCAACTGAGTCCCCAGCACCT SEQ ID NO: 614 RPr GTGGAATGGCAGCTCACTGTAG SEQ ID NO: 615 DHPS NM_013407.1 FPr GGGAGAACGGGATCAATAGGAT SEQ ID NO: 616 Probe CTCATTGGGCACCAGCAGGTTTCC SEQ ID NO: 617 RPr GCATCAGCCAGTCCTCAAACT SEQ ID NO: 618 DIABLO NM_019887.1 FPr CACAATGGCGGCTCTGAAG SEQ ID NO: 619 Probe AAGTTACGCTGCGCGACAGCCAA SEQ ID NO: 620 RPr ACACAAACACTGTCTGTACCTGAAGA SEQ ID NO: 621 DIAPH1 NM_005219.2 FPr CAAGCAGTCAAGGAGAACCA SEQ ID NO: 622 Probe TTCTTCTGTCTCCCGCCGCTTC SEQ ID NO: 623 RPr AGTTTTGCTCGCCTCATCTT SEQ ID NO: 624 DICER1 NM_177438.1 FPr TCCAATTCCAGCATCACTGT SEQ ID NO: 625 Probe AGAAAAGCTGTTTGTCTCCCCAGCA SEQ ID NO: 626 RPr GGCAGTGAAGGCGATAAAGT SEQ ID NO: 627 DKK1 NM_012242.1 FPr TGACAACTACCAGCCGTACC SEQ ID NO: 628 Probe AGTGCCGCACTCCTCGTCCTCT SEQ ID NO: 629 RPr GGGACTAGCGCAGTACTCATC SEQ ID NO: 630 DLC1 NM_006094.3 FPr GATTCAGACGAGGATGAGCC SEQ ID NO: 631 Probe AAAGTCCATTTGCCACTGATGGCA SEQ ID NO: 632 RPr CACCTCTTGCTGTCCCTTTG SEQ ID NO: 633 DPYD NM_000110.2 FPr AGGACGCAAGGAGGGTTTG SEQ ID NO: 634 Probe CAGTGCCTACAGTCTCGAGTCTGCCAGTG SEQ ID NO: 635 RPr GATGTCCGCCGAGTCCTTACT SEQ ID NO: 636 DR4 NM_003844.1 FPr TGCACAGAGGGTGTGGGTTAC SEQ ID NO: 637 Probe CAATGCTTCCAACAATTTGTTTGCTTGCC SEQ ID NO: 638 RPr TCTTCATCTGATTTACAAGCTGTACATG SEQ ID NO: 639 DR5 NM_003842.2 FPr CTCTGAGACAGTGCTTCGATGACT SEQ ID NO: 640 Probe CAGACTTGGTGCCCTTTGACTCC SEQ ID NO: 641 RPr CCATGAGGCCCAACTTCCT SEQ ID NO: 642 DRG1 NM_004147.3 FPr CCTGGATCTCCCAGGTATCA SEQ ID NO: 643 Probe ACCTTTCCCATCCTTGGCACCTTC SEQ ID NO: 644 RPr TGCAATGACTTGACGACCTC SEQ ID NO: 645 DSP NM_004415.1 FPr TGGCACTACTGCATGATTGACA SEQ ID NO: 646 Probe CAGGGCCATGACAATCGCCAA SEQ ID NO: 647 RPr CCTGCCGCATTGTTTTCAG SEQ ID NO: 648 DTYMK NM_012145.1 FPr AAATCGCTGGGAACAAGTG SEQ ID NO: 649 Probe CGCCCTGGCTCAACTTTTCCTTAA SEQ ID NO: 650 RPr AATGCGTATCTGTCCACGAC SEQ ID NO: 651 DUSP1 NM_004417.2 FPr AGACATCAGCTCCTGGTTCA SEQ ID NO: 652 Probe CGAGGCCATTGACTTCATAGACTCCA SEQ ID NO: 653 RPr GACAAACACCCTTCCTCCAG SEQ ID NO: 654 DUSP2 NM_004418.2 FPr TATCCCTGTGGAGGACAACC SEQ ID NO: 655 Probe CCTCCTGGAACCAGGCACTGATCT SEQ ID NO: 656 RPr CACCCAGTCAATGAAGCCTA SEQ ID NO: 657 DUT NM_001948.2 FPr ACACATGGAGTGCTTCTGGA SEQ ID NO: 658 Probe ATCAGCCCACTTGACCACCCAGTT SEQ ID NO: 659 RPr CTCTTGCCTGTGCTTCCAC SEQ ID NO: 660 DYRK1B NM_004714.1 FPr AGCATGACACGGAGATGAAG SEQ ID NO: 661 Probe CACCTGAAGCGGCACTTCATGTTC SEQ ID NO: 662 RPr AATACCAGGCACAGGTGGTT SEQ ID NO: 663 E2F1 NM_005225.1 FPr ACTCCCTCTACCCTTGAGCA SEQ ID NO: 664 Probe CAGAAGAACAGCTCAGGGACCCCT SEQ ID NO: 665 RPr CAGGCCTCAGTTCCTTCAGT SEQ ID NO: 666 EDN1 NM_001955.1 FPr TGCCACCTGGACATCATTTG SEQ ID NO: 667 endothelin Probe CACTCCCGAGCACGTTGTTCCGT SEQ ID NO: 668 RPr TGGACCTAGGGCTTCCAAGTC SEQ ID NO: 669 EFNA1 NM_004428.2 FPr TACATCTCCAAACCCATCCA SEQ ID NO: 670 Probe CAACCTCAAGCAGCGGTCTTCATG SEQ ID NO: 671 RPr TTGCCACTGACAGTCACCTT SEQ ID NO: 672 EFNA3 NM_004952.3 FPr ACTACATCTCCACGCCCACT SEQ ID NO: 673 Probe CCTCAGACACTTCCAGTGCAGGTTG SEQ ID NO: 674 RPr CAGCAGACGAACACCTTCAT SEQ ID NO: 675 EFNB1 NM_004429.3 FPr GGAGCCCGTATCCTGGAG SEQ ID NO: 676 Probe CCCTCAACCCCAAGTTCCTGAGTG SEQ ID NO: 677 RPr GGATAGATCACCAAGCCCTTC SEQ ID NO: 678 EFNB2 NM_004093.2 FPr TGACATTATCATCCCGCTAAGGA SEQ ID NO: 679 Probe CGGACAGCGTCTTCTGCCCTCACT SEQ ID NO: 680 RPr GTAGTCCCCGCTGACCTTCTC SEQ ID NO: 681 EFP NM_005082.2 FPr TTGAACAGAGCCTGACCAAG SEQ ID NO: 682 Probe TGATGCTTTCTCCAGAAACTCGAACTCA SEQ ID NO: 683 RPr TGTTGAGATTCCTCGCAGTT SEQ ID NO: 684 EGFR NM_005228.1 FPr TGTCGATGGACTTCCAGAAC SEQ ID NO: 685 Probe CACCTGGGCAGCTGCCAA SEQ ID NO: 686 RPr ATTGGGACAGCTTGGATCA SEQ ID NO: 687 EGLN1 NM_022051.1 FPr TCAATGGCCGGACGAAAG SEQ ID NO: 688 Probe CATTGCCCGGATAACAAGCAACCATG SEQ ID NO: 689 RPr TTTGGATTATCAACATGACGTACATAAC SEQ ID NO: 690 EGLN3 NM_022073.2 FPr GCTGGTCCTCTACTGCGG SEQ ID NO: 691 Probe CCGGCTGGGCAAATACTACGTCAA SEQ ID NO: 692 RPr CCACCATTGCCTTAGACCTC SEQ ID NO: 693 EGR1 NM_001964.2 FPr GTCCCCGCTGCAGATCTCT SEQ ID NO: 694 Probe CGGATCCTTTCCTCACTCGCCCA SEQ ID NO: 695 RPr CTCCAGCTTAGGGTAGTTGTCCAT SEQ ID NO: 696 EGR3 NM_004430.2 FPr CCATGTGGATGAATGAGGTG SEQ ID NO: 697 Probe ACCCAGTCTCACCTTCTCCCCACC SEQ ID NO: 698 RPr TGCCTGAGAAGAGGTGAGGT SEQ ID NO: 699 EI24 NM_004879.2 FPr AAAGTGGTGAATGCCATTTG SEQ ID NO: 700 Probe CCTCAAATGCCAGGTCAGCTATATCCTG SEQ ID NO: 701 RPr GTGAGGCTTCCTCCCTGATA SEQ ID NO: 702 EIF4E NM_001968.1 FPr GATCTAAGATGGCGACTGTCGAA SEQ ID NO: 703 Probe ACCACCCCTACTCCTAATCCCCCGACT SEQ ID NO: 704 RPr TTAGATTCCGTTTTCTCCTCTTCTG SEQ ID NO: 705 EIF4EL3 NM_004846.1 FPr AAGCCGCGGTTGAATGTG SEQ ID NO: 706 Probe TGACCCTCTCCCTCTCTGGATGGCA SEQ ID NO: 707 RPr TGACGCCAGCTTCAATGATG SEQ ID NO: 708 ELAVL1 NM_001419.2 FPr GACAGGAGGCCTCTATCCTG SEQ ID NO: 709 Probe CACCCCACCCTCCACCTCAATC SEQ ID NO: 710 RPr GTGAGGTAGGTCTGGGGAAG SEQ ID NO: 711 EMP1 NM_001423.1 FPr GCTAGTACTTTGATGCTCCCTTGAT SEQ ID NO: 712 Probe CCAGAGAGCCTCCCTGCAGCCA SEQ ID NO: 713 RPr GAACAGCTGGAGGCCAAGTC SEQ ID NO: 714 EMR3 NM_032571.2 FPr TGGCCTACCTCTTCACCATC SEQ ID NO: 715 Probe TCAACAGCCTCCAAGGCTTCTTCA SEQ ID NO: 716 RPr TGAGGAGGCAGTAGACCAAGA SEQ ID NO: 717 EMS1 NM_005231.2 FPr GGCAGTGTCACTGAGTCCTTGA SEQ ID NO: 718 Probe ATCCTCCCCTGCCCCGCG SEQ ID NO: 719 RPr TGCACTGTGCGTCCCAAT SEQ ID NO: 720 ENO1 NM_001428.2 FPr CAAGGCCGTGAACGAGAAGT SEQ ID NO: 721 Probe CTGCAACTGCCTCCTGCTCAAAGTCA SEQ ID NO: 722 RPr CGGTCACGGAGCCAATCT SEQ ID NO: 723 EP300 NM_001429.1 FPr AGCCCCAGCAACTACAGTCT SEQ ID NO: 724 Probe CACTGACATCATGGCTGGCCTTG SEQ ID NO: 725 RPr TGTTCAAAGGTTGACCATGC SEQ ID NO: 726 EPAS1 NM_001430.3 FPr AAGCCTTGGAGGGTTTCATTG SEQ ID NO: 727 Probe TGTCGCCATCTTGGGTCACCACG SEQ ID NO: 728 RPr TGCTGATGTTTTCTGACAGAAAGAT SEQ ID NO: 729 EpCAM NM_002354.1 FPr GGGCCCTCCAGAACAATGAT SEQ ID NO: 730 Probe CCGCTCTCATCGCAGTCAGGATCAT SEQ ID NO: 731 RPr TGCACTGCTTGGCCTTAAAGA SEQ ID NO: 732 EPHA2 NM_004431.2 FPr CGCCTGTTCACCAAGATTGAC SEQ ID NO: 733 Probe TGCGCCCGATGAGATCACCG SEQ ID NO: 734 RPr GTGGCGTGCCTCGAAGTC SEQ ID NO: 735 EPHB2 NM_004442.4 FPr CAACCAGGCAGCTCCATC SEQ ID NO: 736 Probe CACCTGATGCATGATGGACACTGC SEQ ID NO: 737 RPr GTAATGCTGTCCACGGTGC SEQ ID NO: 738 EPHB4 NM_004444.3 FPr TGAACGGGGTATCCTCCTTA SEQ ID NO: 739 Probe CGTCCCATTTGAGCCTGTCAATGT SEQ ID NO: 740 RPr AGGTACCTCTCGGTCAGTGG SEQ ID NO: 741 EphB6 NM_004445.1 FPr ACTGGTCCTCCATCGGCT SEQ ID NO: 742 Probe CCTTGCACCTCAAACCAAAGCTCC SEQ ID NO: 743 RPr CCAGTGTAGCATGAGTGCTGA SEQ ID NO: 744 EPM2A NM_005670.2 FPr ACTGTGGCACTTAGGGGAGA SEQ ID NO: 745 Probe CTGCCTCTGCCCAAAGCAAATGTC SEQ ID NO: 746 RPr AGTGGAAATGTGTCCTGGCT SEQ ID NO: 747 ErbB3 NM_001982.1 FPr CGGTTATGTCATGCCAGATACAC SEQ ID NO: 748 Probe CCTCAAAGGTACTCCCTCCTCCCGG SEQ ID NO: 749 RPr GAACTGAGACCCACTGAAGAAAGG SEQ ID NO: 750 ERCC1 NM_001983.1 FPr GTCCAGGTGGATGTGAAAGA SEQ ID NO: 751 Probe CAGCAGGCCCTCAAGGAGCTG SEQ ID NO: 752 RPr CGGCCAGGATACACATCTTA SEQ ID NO: 753 ERCC2 NM_000400.2 FPr TGGCCTTCTTCACCAGCTA SEQ ID NO: 754 Probe AGGCCACGGTGCTCTCCATGTACT SEQ ID NO: 755 RPr CAAGGATCCCCTGCTCATAC SEQ ID NO: 756 EREG NM_001432.1 FPr ATAACAAAGTGTAGCTCTGACATGAATG SEQ ID NO: 757 Probe TTGTTTGCATGGACAGTGCATCTATCTGGT SEQ ID NO: 758 RPr CACACCTGCAGTAGTTTTGACTCA SEQ ID NO: 759 ERK1 Z11696.1 FPr ACGGATCACAGTGGAGGAAG SEQ ID NO: 760 Probe CGCTGGCTCACCCCTACCTG SEQ ID NO: 761 RPr CTCATCCGTCGGGTCATAGT SEQ ID NO: 762 ERK2 NM_002745.1 FPr AGTTCTTGACCCCTGGTCCT SEQ ID NO: 763 Probe TCTCCAGCCCGTCTTGGCTT SEQ ID NO: 764 RPr AAACGGCTCAAAGGAGTCAA SEQ ID NO: 765 ESPL1 NM_012291.1 FPr ACCCCCAGACCGGATCAG SEQ ID NO: 766 Probe CTGGCCCTCATGTCCCCTTCACG SEQ ID NO: 767 RPr TGTAGGGCAGACTTCCTCAAACA SEQ ID NO: 768 EstR1 NM_000125.1 FPr CGTGGTGCCCCTCTATGAC SEQ ID NO: 769 Probe CTGGAGATGCTGGACGCCC SEQ ID NO: 770 RPr GGCTAGTGGGCGCATGTAG SEQ ID NO: 771 ETV4 NM_001986.1 FPr TCCAGTGCCTATGACCCC SEQ ID NO: 772 Probe CAGACAAATCGCCATCAAGTCCCC SEQ ID NO: 773 RPr ACTGTCCAAGGGCACCAG SEQ ID NO: 774 F3 NM_001993.2 FPr GTGAAGGATGTGAAGCAGACGTA SEQ ID NO: 775 Probe TGGCACGGGTCTTCTCCTACC SEQ ID NO: 776 RPr AACCGGTGCTCTCCACATTC SEQ ID NO: 777 FABP4 NM_001442.1 FPr GCTTTGCCACCAGGAAAGT SEQ ID NO: 778 Probe CTGGCATGGCCAAACCTAACATGA SEQ ID NO: 779 RPr CATCCCCATTCACACTGATG SEQ ID NO: 780 FAP NM_004460.2 FPr CTGACCAGAACCACGGCT SEQ ID NO: 781 Probe CGGCCTGTCCACGAACCACTTATA SEQ ID NO: 782 RPr GGAAGTGGGTCATGTGGG SEQ ID NO: 783 fas NM_000043.1 FPr GGATTGCTCAACAACCATGCT SEQ ID NO: 784 Probe TCTGGACCCTCCTACCTCTGGTTCTTACGCT SEQ ID NO: 785 RPr GGCATTAACACTTTTGGACGATAA SEQ ID NO: 786 fasl NM_000639.1 FPr GCACTTTGGGATTCTTTCCATTAT SEQ ID NO: 787 Probe ACAACATTCTCGGTGCCTGTAACAAAGAA SEQ ID NO: 788 RPr GCATGTAAGAAGACCCTCACTGAA SEQ ID NO: 789 FASN NM_004104.4 FPr GCCTCTTCCTGTTCGACG SEQ ID NO: 790 Probe TCGCCCACCTACGTACTGGCCTAC SEQ ID NO: 791 RPr GCTTTGCCCGGTAGCTCT SEQ ID NO: 792 FBXO5 NM_012177.2 FPr GGCTATTCCTCATTTTCTCTACAAAGTG SEQ ID NO: 793 Probe CCTCCAGGAGGCTACCTTCTTCATGTTCAC SEQ ID NO: 794 RPr GGATTGTAGACTGTCACCGAAATTC SEQ ID NO: 795 FBXW7 NM_033632.1 FPr CCCCAGTTTCAACGAGACTT SEQ ID NO: 796 Probe TCATTGCTCCCTAAAGAGTTGGCACTC SEQ ID NO: 797 RPr GTTCCAGGAATGAAAGCACA SEQ ID NO: 798 FDXR NM_004110.2 FPr GAGATGATTCAGTTACCGGGAG SEQ ID NO: 799 Probe AATCCACAGGATCCAAAATGGGCC SEQ ID NO: 800 RPr ATCTTGTCCTGGAGACCCAA SEQ ID NO: 801 FES NM_002005.2 FPr CTCTGCAGGCCTAGGTGC SEQ ID NO: 802 Probe CTCCTCAGCGGCTCCAGCTCATAT SEQ ID NO: 803 RPr CCAGGACTGTGAAGAGCTGTC SEQ ID NO: 804 FGF18 NM_003862.1 FPr CGGTAGTCAAGTCCGGATCAA SEQ ID NO: 805 Probe CAAGGAGACGGAATTCTACCTGTGC SEQ ID NO: 806 RPr GCTTGCCTTTGCGGTTCA SEQ ID NO: 807 FGF2 NM_002006.2 FPr AGATGCAGGAGAGAGGAAGC SEQ ID NO: 808 Probe CCTGCAGACTGCTTTTTGCCCAAT SEQ ID NO: 809 RPr GTTTTGCAGCCTTACCCAAT SEQ ID NO: 810 FGFR1 NM_023109.1 FPr CACGGGACATTCACCACATC SEQ ID NO: 811 Probe ATAAAAAGACAACCAACGGCCGACTGC SEQ ID NO: 812 RPr GGGTGCCATCCACTTCACA SEQ ID NO: 813 FGFR2 NM_000141.2 FPr GAGGGACTGTTGGCATGCA SEQ ID NO: 814 isoform 1 Probe TCCCAGAGACCAACGTTCAAGCAGTTG SEQ ID NO: 815 RPr GAGTGAGAATTCGATCCAAGTCTTC SEQ ID NO: 816 FHIT NM_002012.1 FPr CCAGTGGAGCGCTTCCAT SEQ ID NO: 817 Probe TCGGCCACTTCATCAGGACGCAG SEQ ID NO: 818 RPr CTCTCTGGGTCGTCTGAAACAA SEQ ID NO: 819 FIGF NM_004469.2 FPr GGTTCCAGCTTTCTGTAGCTGT SEQ ID NO: 820 Probe ATTGGTGGCCACACCACCTCCTTA SEQ ID NO: 821 RPr GCCGCAGGTTCTAGTTGCT SEQ ID NO: 822 FLJ12455 NM_022078.1 FPr CCACCAGCATGAAGTTTCG SEQ ID NO: 823 Probe ACCCCTCACAAAGGCCATGTCTGT SEQ ID NO: 824 RPr GGCTGTCTGAAGCACAACTG SEQ ID NO: 825 FLJ20712 AK000719.1 FPr GCCACACAAACATGCTCCT SEQ ID NO: 826 Probe ATGTCTTTCCCAGCAGCTCTGCCT SEQ ID NO: 827 RPr GCCACAGGAAACTTCCGA SEQ ID NO: 828 FLT1 NM_002019.1 FPr GGCTCCCGAATCTATCTTTG SEQ ID NO: 829 Probe CTACAGCACCAAGAGCGACGTGTG SEQ ID NO: 830 RPr TCCCACAGCAATACTCCGTA SEQ ID NO: 831 FLT4 NM_002020.1 FPr ACCAAGAAGCTGAGGACCTG SEQ ID NO: 832 Probe AGCCCGCTGACCATGGAAGATCT SEQ ID NO: 833 RPr CCTGGAAGCTGTAGCAGACA SEQ ID NO: 834 FOS NM_005252.2 FPr CGAGCCCTTTGATGACTTCCT SEQ ID NO: 835 Probe TCCCAGCATCATCCAGGCCCAG SEQ ID NO: 836 RPr GGAGCGGGCTGTCTCAGA SEQ ID NO: 837 FOXO3A NM_001455.1 FPr TGAAGTCCAGGACGATGATG SEQ ID NO: 838 Probe CTCTACAGCAGCTCAGCCAGCCTG SEQ ID NO: 839 RPr ACGGCTTGCTTACTGAAGGT SEQ ID NO: 840 FPGS NM_004957.3 FPr CAGCCCTGCCAGTTTGAC SEQ ID NO: 841 Probe ATGCCGTCTTCTGCCCTAACCTGA SEQ ID NO: 842 RPr GTTGCCTGTGGATGACACC SEQ ID NO: 843 FRP1 NM_003012.2 FPr TTGGTACCTGTGGGTTAGCA SEQ ID NO: 844 Probe TCCCCAGGGTAGAATTCAATCAGAGC SEQ ID NO: 845 RPr CACATCCAAATGCAAACTGG SEQ ID NO: 846 FST NM_006350.2 FPr GTAAGTCGGATGAGCCTGTCTGT SEQ ID NO: 847 Probe CCAGTGACAATGCCACTTATGCCAGC SEQ ID NO: 848 RPr CAGCTTCCTTCATGGCACACT SEQ ID NO: 849 Furin NM_002569.1 FPr AAGTCCTCGATACGCACTATAGCA SEQ ID NO: 850 Probe CCCGGATGGTCTCCACGTCAT SEQ ID NO: 851 RPr CTGGCATGTGGCACATGAG SEQ ID NO: 852 FUS NM_004960.1 FPr GGATAATTCAGACAACAACACCATCT SEQ ID NO: 853 Probe TCAATTGTAACATTCTCACCCAGGCCTTG SEQ ID NO: 854 RPr TGAAGTAATCAGCCACAGACTCAAT SEQ ID NO: 855 FUT1 NM_000148.1 FPr CCGTGCTCATTGCTAACCA SEQ ID NO: 856 Probe TCTGTCCCTGAACTCCCAGAACCA SEQ ID NO: 857 RPr CTGCCCAAAGCCAGATGTA SEQ ID NO: 858 FUT3 NM_000149.1 FPr CAGTTCGGTCCAACAGAGAA SEQ ID NO: 859 Probe AGCAGGCAACCACCATGTCATTTG SEQ ID NO: 860 RPr TGCGAATTATATCCCGATGA SEQ ID NO: 861 FUT6 NM_000150.1 FPr CGTGTGTCTCAAGACGATCC SEQ ID NO: 862 Probe TGTGTACCCTAATGGGTCCCGCTT SEQ ID NO: 863 RPr GGTCCCTGTGCTGTCTGG SEQ ID NO: 864 FXYD5 NM_014164.4 FPr AGAGCACCAAAGCAGCTCAT SEQ ID NO: 865 Probe CACTGATGACACCACGACGCTCTC SEQ ID NO: 866 RPr GTGCTTGGGGATGGTCTCT SEQ ID NO: 867 FYN NM_002037.3 FPr GAAGCGCAGATCATGAAGAA SEQ ID NO: 868 Probe CTGAAGCACGACAAGCTGGTCCAG SEQ ID NO: 869 RPr CTCCTCAGACACCACTGCAT SEQ ID NO: 870 FZD1 NM_003505.1 FPr GGTGCACCAGTTCTACCCTC SEQ ID NO: 871 Probe ACTTGAGCTCAGCGGAACACTGCA SEQ ID NO: 872 RPr GCGTACATGGAGCACAGGA SEQ ID NO: 873 FZD2 NM_001466.2 FPr TGGATCCTCACCTGGTCG SEQ ID NO: 874 Probe TGCGCTTCCACCTTCTTCACTGTC SEQ ID NO: 875 RPr GCGCTGCATGTCTACCAA SEQ ID NO: 876 FZD6 NM_003506.2 FPr AATGAGAGAGGTGAAAGCGG SEQ ID NO: 877 Probe CGGAGCTAGCACCCCCAGGTTAAG SEQ ID NO: 878 RPr AGGTTCACCACAGTCCTGTTC SEQ ID NO: 879 G-Catenin NM_002230.1 FPr TCAGCAGCAAGGGCATCAT SEQ ID NO: 880 Probe CGCCCGCAGGCCTCATCCT SEQ ID NO: 881 RPr GGTGGTTTTCTTGAGCGTGTACT SEQ ID NO: 882 G1P2 NM_005101.1 FPr CAACGAATTCCAGGTGTCC SEQ ID NO: 883 Probe CTGAGCAGCTCCATGTCGGTGTC SEQ ID NO: 884 RPr GATCTGCGCCTTCAGCTC SEQ ID NO: 885 GADD45 NM_001924.2 FPr GTGCTGGTGACGAATCCA SEQ ID NO: 886 Probe TTCATCTCAATGGAAGGATCCTGCC SEQ ID NO: 887 RPr CCCGGCAAAAACAAATAAGT SEQ ID NO: 888 GADD45B NM_015675.1 FPr ACCCTCGACAAGACCACACT SEQ ID NO: 889 Probe AACTTCAGCCCCAGCTCCCAAGTC SEQ ID NO: 890 RPr TGGGAGTTCATGGGTACAGA SEQ ID NO: 891 GADD45G NM_006705.2 FPr CGCGCTGCAGATCCATTT SEQ ID NO: 892 Probe CGCTGATCCAGGCTTTCTGCTGC SEQ ID NO: 893 RPr CGCACTATGTCGATGTCGTTCT SEQ ID NO: 894 GAGE4 NM_001474.1 FPr GGAACAGGGTCACCCACAGA SEQ ID NO: 895 Probe TCAGGACCATCTTCACACTCACACCCA SEQ ID NO: 896 RPr GATTTGGCGGGTCCATCTC SEQ ID NO: 897 GBP1 NM_002053.1 FPr TTGGGAAATATTTGGGCATT SEQ ID NO: 898 Probe TTGGGACATTGTAGACTTGGCCAGAC SEQ ID NO: 899 RPr AGAAGCTAGGGTGGTTGTCC SEQ ID NO: 900 GBP2 NM_004120.2 FPr GCATGGGAACCATCAACCA SEQ ID NO: 901 Probe CCATGGACCAACTTCACTATGTGACAGA SEQ ID NO: 902 GC RPr TGAGGAGTTTGCCTTGATTCG SEQ ID NO: 903 GCLC NM_001498.1 FPr CTGTTGCAGGAAGGCATTGA SEQ ID NO: 904 Probe CATCTCCTGGCCCAGCATGTT SEQ ID NO: 905 RPr GTCAGTGGGTCTCTAATAAAGAGATGAG SEQ ID NO: 906 GCLM NM_002061.1 FPr TGTAGAATCAAACTCTTCATCATCAACT SEQ ID NO: 907 AG Probe TGCAGTTGACATGGCCTGTTCAGTCC SEQ ID NO: 908 RPr CACAGAATCCAGCTGTGCAACT SEQ ID NO: 909 GCNT1 NM_001490.3 FPr TGGTGCTTGGAGCATAGAAG SEQ ID NO: 910 Probe TGCCCTTCACAAAGGAAATCCCTG SEQ ID NO: 911 RPr GCAACGTCCTCAGCATTTC SEQ ID NO: 912 GDF15 NM_004864.1 FPr CGCTCCAGACCTATGATGACT SEQ ID NO: 913 Probe TGTTAGCCAAAGACTGCCACTGCA SEQ ID NO: 914 RPr ACAGTGGAAGGACCAGGACT SEQ ID NO: 915 GIT1 NM_014030.2 FPr GTGTATGACGAGGTGGATCG SEQ ID NO: 916 Probe AGCCAGCCACACTGCATCATTTTC SEQ ID NO: 917 RPr ACCAGAGTGCTGTGGTTTTG SEQ ID NO: 918 GJA1 NM_000165.2 FPr GTTCACTGGGGGTGTATGG SEQ ID NO: 919 Probe ATCCCCTCCCTCTCCACCCATCTA SEQ ID NO: 920 RPr AAATACCAACATGCACCTCTCTT SEQ ID NO: 921 GJB2 NM_004004.3 FPr TGTCATGTACGACGGCTTCT SEQ ID NO: 922 Probe AGGCGTTGCACTTCACCAGCC SEQ ID NO: 923 RPr AGTCCACAGTGTTGGGACAA SEQ ID NO: 924 GPX1 NM_000581.2 FPr GCTTATGACCGACCCCAA SEQ ID NO: 925 Probe CTCATCACCTGGTCTCCGGTGTGT SEQ ID NO: 926 RPr AAAGTTCCAGGCAACATCGT SEQ ID NO: 927 GPX2 NM_002083.1 FPr CACACAGATCTCCTACTCCATCCA SEQ ID NO: 928 Probe CATGCTGCATCCTAAGGCTCCTCAGG SEQ ID NO: 929 RPr GGTCCAGCAGTGTCTCCTGAA SEQ ID NO: 930 Grb10 NM_005311.2 FPr CTTCGCCTTTGCTGATTGC SEQ ID NO: 931 Probe CTCCAAACGCCTGCCTGACGACTG SEQ ID NO: 932 RPr CCATAACGCACATGCTCCAA SEQ ID NO: 933 GRB14 NM_004490.1 FPr TCCCACTGAAGCCCTTTCAG SEQ ID NO: 934 Probe CCTCCAAGCGAGTCCTTCTTCAACCG SEQ ID NO: 935 RPr AGTGCCCAGGCGTAAACATC SEQ ID NO: 936 GRB2 NM_002086.2 FPr GTCCATCAGTGCATGACGTT SEQ ID NO: 937 Probe AGGCCACGTATAGTCCTAGCTGACGC SEQ ID NO: 938 RPr AGCCCACTTGGTTTCTTGTT SEQ ID NO: 939 GRB7 NM_005310.1 FPr CCATCTGCATCCATCTTGTT SEQ ID NO: 940 Probe CTCCCCACCCTTGAGAAGTGCCT SEQ ID NO: 941 RPr GGCCACCAGGGTATTATCTG SEQ ID NO: 942 GRIK1 NM_000830.2 FPr GTTGGGTGCATCTCTCGG SEQ ID NO: 943 Probe AATTCATGCCGAGATACAGCCGCT SEQ ID NO: 944 RPr CGTGCTCCATCTTCCTAGCTT SEQ ID NO: 945 GRO1 NM_001511.1 FPr CGAAAAGATGCTGAACAGTGACA SEQ ID NO: 946 Probe CTTCCTCCTCCCTTCTGGTCAGTTGGAT SEQ ID NO: 947 RPr TCAGGAACAGCCACCAGTGA SEQ ID NO: 948 GRP NM_002091.1 FPr CTGGGTCTCATAGAAGCAAAGGA SEQ ID NO: 949 Probe AGAAACCACCAGCCACCTCAACCCA SEQ ID NO: 950 RPr CCACGAAGGCTGCTGATTG SEQ ID NO: 951 GRPR NM_005314.1 FPr ATGCTGCTGGCCATTCCA SEQ ID NO: 952 Probe CCGTGTTTTCTGACCTCCATCCCTTCC SEQ ID NO: 953 RPr AGGTCTGGTTGGTGCTTTCCT SEQ ID NO: 954 GSK3B NM_002093.2 FPr GACAAGGACGGCAGCAAG SEQ ID NO: 955 Probe CCAGGAGTTGCCACCACTGTTGTC SEQ ID NO: 956 RPr TTGTGGCCTGTCTGGACC SEQ ID NO: 957 GSTA3 NM_000847.3 FPr TCTCCAACTTCCCTCTGCTG SEQ ID NO: 958 Probe AGGCCCTGAAAACCAGAATCAGCA SEQ ID NO: 959 RPr ACTTCTTCACCGTGGGCA SEQ ID NO: 960 GSTM1 NM_000561.1 FPr AAGCTATGAGGAAAAGAAGTACACGAT SEQ ID NO: 961 Probe TCAGCCACTGGCTTCTGTCATAATCAGG SEQ ID NO: 962 AG RPr GGCCCAGCTTGAATTTTTCA SEQ ID NO: 963 GSTM3 NM_000849.3 FPr CAATGCCATCTTGCGCTACAT SEQ ID NO: 964 Probe CTCGCAAGCACAACATGTGTGGTGAGA SEQ ID NO: 965 RPr GTCCACTCGAATCTTTTCTTCTTCA SEQ ID NO: 966 GSTp NM_000852.2 FPr GAGACCCTGCTGTCCCAGAA SEQ ID NO: 967 Probe TCCCACAATGAAGGTCTTGCCTCCCT SEQ ID NO: 968 RPr GGTTGTAGTCAGCGAAGGAGATC SEQ ID NO: 969 GSTT1 NM_000853.1 FPr CACCATCCCCACCCTGTCT SEQ ID NO: 970 Probe CACAGCCGCCTGAAAGCCACAAT SEQ ID NO: 971 RPr GGCCTCAGTGTGCATCATTCT SEQ ID NO: 972 H2AFZ NM_002106.2 FPr CCGGAAAGGCCAAGACAA SEQ ID NO: 973 Probe CCCGCTCGCAGAGAGCCGG SEQ ID NO: 974 RPr AATACGGCCCACTGGGAACT SEQ ID NO: 975 HB-EGF NM_001945.1 FPr GACTCCTTCGTCCCCAGTTG SEQ ID NO: 976 Probe TTGGGCCTCCCATAATTGCTTTGCC SEQ ID NO: 977 RPr TGGCACTTGAAGGCTCTGGTA SEQ ID NO: 978 hCRA a U78556.1 FPr TGACACCCTTACCTTCCTGAGAA SEQ ID NO: 979 Probe TCTGCTTTCCGCGCTCCCAGG SEQ ID NO: 980 RPr AAAAACACGAGTCAAAAATAGAAGTCA SEQ ID NO: 981 CT HDAC1 NM_004964.2 FPr CAAGTACCACAGCGATGACTACATTAA SEQ ID NO: 982 Probe TTCTTGCGCTCCATCCGTCCAGA SEQ ID NO: 983 RPr GCTTGCTGTACTCCGACATGTT SEQ ID NO: 984 HDAC2 NM_001527.1 FPr GGTGGCTACACAATCCGTAA SEQ ID NO: 985 Probe TGCAGTCTCATATGTCCAACATCGAGC SEQ ID NO: 986 RPr TGGGAATCTCACAATCAAGG SEQ ID NO: 987 HDGF NM_004494.1 FPr TCCTAGGCATTCTGGACCTC SEQ ID NO: 988 Probe CATTCCTACCCCTGATCCCAACCC SEQ ID NO: 989 RPr GCTGTTGATGCTCCATCCTT SEQ ID NO: 990 hENT1 NM_004955.1 FPr AGCCGTGACTGTTGAGGTC SEQ ID NO: 991 Probe AAGTCCAGCATCGCAGGCAGC SEQ ID NO: 992 RPr AAGTAACGTTCCCAGGTGCT SEQ ID NO: 993 Hepsin NM_002151.1 FPr AGGCTGCTGGAGGTCATCTC SEQ ID NO: 994 Probe CCAGAGGCCGTTTCTTGGCCG SEQ ID NO: 995 RPr CTTCCTGCGGCCACAGTCT SEQ ID NO: 996 HER2 NM_004448.1 FPr CGGTGTGAGAAGTGCAGCAA SEQ ID NO: 997 Probe CCAGACCATAGCACACTCGGGCAC SEQ ID NO: 998 RPr CCTCTCGCAAGTGCTCCAT SEQ ID NO: 999 Herstatin AF177761.2 FPr CACCCTGTCCTATCCTTCCT SEQ ID NO: 1000 Probe CCCTCTTGGGACCTAGTCTCTGCCT SEQ ID NO: 1001 RPr GGCCAGGGGTAGAGAGTAGA SEQ ID NO: 1002 HES6 NM_018645.3 FPr TTAGGGACCCTGCAGCTCT SEQ ID NO: 1003 Probe TAGCTCCCTCCCTCCACCCACTC SEQ ID NO: 1004 RPr CTACAAAATTCTTCCTCCTGCC SEQ ID NO: 1005 HGF M29145.1 FPr CCGAAATCCAGATGATGATG SEQ ID NO: 1006 Probe CTCATGGACCCTGGTGCTACACG SEQ ID NO: 1007 RPr CCCAAGGAATGAGTGGATTT SEQ ID NO: 1008 HIF1A NM_001530.1 FPr TGAACATAAAGTCTGCAACATGGA SEQ ID NO: 1009 Probe TTGCACTGCACAGGCCACATTCAC SEQ ID NO: 1010 RPr TGAGGTTGGTTACTGTTGGTATCATATA SEQ ID NO: 1011 HK1 NM_000188.1 FPr TACGCACAGAGGCAAGCA SEQ ID NO: 1012 Probe TAAGAGTCCGGGATCCCCAGCCTA SEQ ID NO: 1013 RPr GAGAGAAGTGCTGGAGAGGC SEQ ID NO: 1014 HLA-DPB1 NM_002121.4 FPr TCCATGATGGTTCTGCAGGTT SEQ ID NO: 1015 Probe CCCCGGACAGTGGCTCTGACG SEQ ID NO: 1016 RPr TGAGCAGCACCATCAGTAACG SEQ ID NO: 1017 HLA-DRA NM_019111.3 FPr GACGATTTGCCAGCTTTGAG SEQ ID NO: 1018 Probe TCAAGGTGCATTGGCCAACATAGC SEQ ID NO: 1019 RPr TCCAGGTTGGCTTTGTCC SEQ ID NO: 1020 HLA-DRB1 NM_002124.1 FPr GCTTTCTCAGGACCTGGTTG SEQ ID NO: 1021 Probe CATTTTCTGCAGTTGCCGAACCAG SEQ ID NO: 1022 RPr AGGAAGCCACAAGGGAGG SEQ ID NO: 1023 HLA-G NM_002127.2 FPr CCTGCGCGGCTACTACAAC SEQ ID NO: 1024 Probe CGAGGCCAGTTCTCACACCCTCCAG SEQ ID NO: 1025 RPr CAGGTCGCAGCCAATCATC SEQ ID NO: 1026 HMGB1 NM_002128.3 FPr TGGCCTGTCCATTGGTGAT SEQ ID NO: 1027 Probe TTCCACATCTCTCCCAGTTTCTTCGCAA SEQ ID NO: 1028 RPr GCTTGTCATCTGCAGCAGTGTT SEQ ID NO: 1029 hMLH NM_000249.2 FPr CTACTTCCAGCAACCCCAGA SEQ ID NO: 1030 Probe TCCACATCAGAATCTTCCCG SEQ ID NO: 1031 RPr CTTTCGGGAATCATCTTCCA SEQ ID NO: 1032 HNRPAB NM_004499.2 FPr CAAGGGAGCGACCAACTGA SEQ ID NO: 1033 Probe CTCCATATCCAAACAAAGCATGTGTGCG SEQ ID NO: 1034 RPr GTTTGCCAAGTTAAATTTGGTACATAAT SEQ ID NO: 1035 HNRPD NM_031370.2 FPr GCCAGTAAGAACGAGGAGGA SEQ ID NO: 1036 Probe AAGGCCATTCAAACTCCTCCCCAC SEQ ID NO: 1037 RPr CGTCGCTGCTTCAGAGTGT SEQ ID NO: 1038 HoxA1 NM_005522.3 FPr AGTGACAGATGGACAATGCAAGA SEQ ID NO: 1039 Probe TGAACTCCTTCCTGGAATACCCCA SEQ ID NO: 1040 RPr CCGAGTCGCCACTGCTAAGT SEQ ID NO: 1041 HoxA5 NM_019102.2 FPr TCCCTTGTGTTCCTTCTGTGAA SEQ ID NO: 1042 Probe AGCCCTGTTCTCGTTGCCCTAATTCATC SEQ ID NO: 1043 RPr GGCAATAAACAGGCTCATGATTAA SEQ ID NO: 1044 HOXB13 NM_006361.2 FPr CGTGCCTTATGGTTACTTTGG SEQ ID NO: 1045 Probe ACACTCGGCAGGAGTAGTACCCGC SEQ ID NO: 1046 RPr CACAGGGTTTCAGCGAGC SEQ ID NO: 1047 HOXB7 NM_004502.2 FPr CAGCCTCAAGTTCGGTTTTC SEQ ID NO: 1048 Probe ACCGGAGCCTTCCCAGAACAAACT SEQ ID NO: 1049 RPr GTTGGAAGCAAACGCACA SEQ ID NO: 1050 HRAS NM_005343.2 FPr GGACGAATACGACCCCACT SEQ ID NO: 1051 Probe ACCACCTGCTTCCGGTAGGAATCC SEQ ID NO: 1052 RPr GCACGTCTCCCCATCAAT SEQ ID NO: 1053 HSBP1 NM_001537.1 FPr GGAGATGGCCGAGACTGAC SEQ ID NO: 1054 Probe CAAGACCGTGCAGGACCTCACCT SEQ ID NO: 1055 RPr CTGCAGGAGTGTCTGCACC SEQ ID NO: 1056 HSD17B1 NM_000413.1 FPr CTGGACCGCACGGACATC SEQ ID NO: 1057 Probe ACCGCTTCTACCAATACCTCGCCCA SEQ ID NO: 1058 RPr CGCCTCGCGAAAGACTTG SEQ ID NO: 1059 HSD17B2 NM_002153.1 FPr GCTTTCCAAGTGGGGAATTA SEQ ID NO: 1060 Probe AGTTGCTTCCATCCAACCTGGAGG SEQ ID NO: 1061 RPr TGCCTGCGATATTTGTTAGG SEQ ID NO: 1062 HSPA1A NM_005345.4 FPr CTGCTGCGACAGTCCACTA SEQ ID NO: 1063 Probe AGAGTGACTCCCGTTGTCCCAAGG SEQ ID NO: 1064 RPr CAGGTTCGCTCTGGGAAG SEQ ID NO: 1065 HSPA1B NM_005346.3 FPr GGTCCGCTTCGTCTTTCGA SEQ ID NO: 1066 Probe TGACTCCCGCGGTCCCAAGG SEQ ID NO: 1067 RPr GCACAGGTTCGCTCTGGAA SEQ ID NO: 1068 HSPA4 NM_002154.3 FPr TTCAGTGTGTCCAGTGCATC SEQ ID NO: 1069 Probe CATTTTCCTCAGACTTGTGAACCTCCACT SEQ ID NO: 1070 RPr ATCTGTTTCCATTGGCTCCT SEQ ID NO: 1071 HSPA5 NM_005347.2 FPr GGCTAGTAGAACTGGATCCCAACA SEQ ID NO: 1072 Probe TAATTAGACCTAGGCCTCAGCTGCACTG SEQ ID NO: 1073 CC RPr GGTCTGCCCAAATGCTTTTC SEQ ID NO: 1074 HSPA8 NM_006597.3 FPr CCTCCCTCTGGTGGTGCTT SEQ ID NO: 1075 Probe CTCAGGGCCCACCATTGAAGAGGTTG SEQ ID NO: 1076 RPr GCTACATCTACACTTGGTTGGCTTAA SEQ ID NO: 1077 HSPB1 NM_001540.2 FPr CCGACTGGAGGAGCATAAA SEQ ID NO: 1078 Probe CGCACTTTTCTGAGCAGACGTCCA SEQ ID NO: 1079 RPr ATGCTGGCTGACTCTGCTC SEQ ID NO: 1080 HSPCA NM_005348.2 FPr CAAAAGGCAGAGGCTGATAA SEQ ID NO: 1081 Probe TGACCAGATCCTTCACAGACTTGTCGT SEQ ID NO: 1082 RPr AGCGCAGTTTCATAAAGCAA SEQ ID NO: 1083 HSPE1 NM_002157.1 FPr GCAAGCAACAGTAGTCGCTG SEQ ID NO: 1084 Probe TCTCCACCCTTTCCTTTAGAACCCG SEQ ID NO: 1085 RPr CCAACTTTCACGCTAACTGGT SEQ ID NO: 1086 HSPG2 NM_005529.2 FPr GAGTACGTGTGCCGAGTGTT SEQ ID NO: 1087 Probe CAGCTCCGTGCCTCTAGAGGCCT SEQ ID NO: 1088 RPr CTCAATGGTGACCAGGACA SEQ ID NO: 1089 ICAM1 NM_000201.1 FPr GCAGACAGTGACCATCTACAGCTT SEQ ID NO: 1090 Probe CCGGCGCCCAACGTGATTCT SEQ ID NO: 1091 RPr CTTCTGAGACCTCTGGCTTCGT SEQ ID NO: 1092 ICAM2 NM_000873.2 FPr GGTCATCCTGACACTGCAAC SEQ ID NO: 1093 Probe TTGCCCACAGCCACCAAAGTG SEQ ID NO: 1094 RPr TGCACTCAATGGTGAAGGAC SEQ ID NO: 1095 ID1 NM_002165.1 FPr AGAACCGCAAGGTGAGCAA SEQ ID NO: 1096 Probe TGGAGATTCTCCAGCACGTCATCGAC SEQ ID NO: 1097 RPr TCCAACTGAAGGTCCCTGATG SEQ ID NO: 1098 ID2 NM_002166.1 FPr AACGACTGCTACTCCAAGCTCAA SEQ ID NO: 1099 Probe TGCCCAGCATCCCCCAGAACAA SEQ ID NO: 1100 RPr GGATTTCCATCTTGCTCACCTT SEQ ID NO: 1101 ID3 NM_002167.2 FPr CTTCACCAAATCCCTTCCTG SEQ ID NO: 1102 Probe TCACAGTCCTTCGCTCCTGAGCAC SEQ ID NO: 1103 RPr CTCTGGCTCTTCAGGCTACA SEQ ID NO: 1104 ID4 NM_001546.2 FPr TGGCCTGGCTCTTAATTTG SEQ ID NO: 1105 Probe CTTTTGTTTTGCCCAGTATAGACTCGGAAG SEQ ID NO: 1106 RPr TGCAATCATGCAAGACCAC SEQ ID NO: 1107 IFIT1 NM_001548.1 FPr TGACAACCAAGCAAATGTGA SEQ ID NO: 1108 Probe AAGTTGCCCCAGGTCACCAGACTC SEQ ID NO: 1109 RPr CAGTCTGCCCATGTGGTAAT SEQ ID NO: 1110 IGF1 NM_000618.1 FPr TCCGGAGCTGTGATCTAAGGA SEQ ID NO: 1111 Probe TGTATTGCGCACCCCTCAAGCCTG SEQ ID NO: 1112 RPr CGGACAGAGCGAGCTGACTT SEQ ID NO: 1113 IGF1R NM_000875.2 FPr GCATGGTAGCCGAAGATTTCA SEQ ID NO: 1114 Probe CGCGTCATACCAAAATCTCCGATTTTGA SEQ ID NO: 1115 RPr TTTCCGGTAATAGTCTGTCTCATAGATATC SEQ ID NO: 1116 IGF2 NM_000612.2 FPr CCGTGCTTCCGGACAACTT SEQ ID NO: 1117 Probe TACCCCGTGGGCAAGTTCTTCCAA SEQ ID NO: 1118 RPr TGGACTGCTTCCAGGTGTCA SEQ ID NO: 1119 IGFBP2 NM_000597.1 FPr GTGGACAGCACCATGAACA SEQ ID NO: 1120 Probe CTTCCGGCCAGCACTGCCTC SEQ ID NO: 1121 RPr CCTTCATACCCGACTTGAGG SEQ ID NO: 1122 IGFBP3 NM_000598.1 FPr ACGCACCGGGTGTCTGA SEQ ID NO: 1123 Probe CCCAAGTTCCACCCCCTCCATTCA SEQ ID NO: 1124 RPr TGCCCTTTCTTGATGATGATTATC SEQ ID NO: 1125 IGFBP5 NM_000599.1 FPr TGGACAAGTACGGGATGAAGCT SEQ ID NO: 1126 Probe CCCGTCAACGTACTCCATGCCTGG SEQ ID NO: 1127 RPr CGAAGGTGTGGCACTGAAAGT SEQ ID NO: 1128 IGFBP6 NM_002178.1 FPr TGAACCGCAGAGACCAACAG SEQ ID NO: 1129 Probe ATCCAGGCACCTCTACCACGCCCTC SEQ ID NO: 1130 RPr GTCTTGGACACCCGCAGAAT SEQ ID NO: 1131 IGFBP7 NM_001553 FPr GGGTCACTATGGAGTTCAAAGGA SEQ ID NO: 1132 Probe CCCGGTCACCAGGCAGGAGTTCT SEQ ID NO: 1133 RPr GGGTCTGAATGGCCAGGTT SEQ ID NO: 1134 IHH NM_002181.1 FPr AAGGACGAGGAGAACACAGG SEQ ID NO: 1135 Probe ATGACCCAGCGCTGCAAGGAC SEQ ID NO: 1136 RPr AGATAGCCAGCGAGTTCAGG SEQ ID NO: 1137 IL-8 NM_000584.2 FPr AAGGAACCATCTCACTGTGTGTAAAC SEQ ID NO: 1138 Probe TGACTTCCAAGCTGGCCGTGGC SEQ ID NO: 1139 RPr ATCAGGAAGGCTGCCAAGAG SEQ ID NO: 1140 IL10 NM_000572.1 FPr GGCGCTGTCATCGATTTCTT SEQ ID NO: 1141 Probe CTGCTCCACGGCCTTGCTCTTG SEQ ID NO: 1142 RPr TGGAGCTTATTAAAGGCATTCTTCA SEQ ID NO: 1143 IL1B NM_000576.2 FPr AGCTGAGGAAGATGCTGGTT SEQ ID NO: 1144 Probe TGCCCACAGACCTTCCAGGAGAAT SEQ ID NO: 1145 RPr GGAAAGAAGGTGCTCAGGTC SEQ ID NO: 1146 IL6 NM_000600.1 FPr CCTGAACCTTCCAAAGATGG SEQ ID NO: 1147 Probe CCAGATTGGAAGCATCCATCTTTTTCA SEQ ID NO: 1148 RPr ACCAGGCAAGTCTCCTCATT SEQ ID NO: 1149 IL6ST NM_002184.2 FPr GGCCTAATGTTCCAGATCCT SEQ ID NO: 1150 Probe CATATTGCCCAGTGGTCACCTCACA SEQ ID NO: 1151 RPr AAAATTGTGCCTTGGAGGAG SEQ ID NO: 1152 ILT-2 NM_006669.1 FPr AGCCATCACTCTCAGTGCAG SEQ ID NO: 1153 Probe CAGGTCCTATCGTGGCCCCTGA SEQ ID NO: 1154 RPr ACTGCAGAGTCAGGGTCTCC SEQ ID NO: 1155 IMP-1 NM_006546.2 FPr GAAAGTGTTTGCGGAGCAC SEQ ID NO: 1156 Probe CTCCTACAGCGGCCAGTTCTTGGT SEQ ID NO: 1157 RPr GAAGGCGTAGCCGGATTT SEQ ID NO: 1158 IMP2 NM_006548.3 FPr CAATCTGATCCCAGGGTTGAA SEQ ID NO: 1159 Probe CTCAGCGCACTTGGCATCTTTTCAACA SEQ ID NO: 1160 RPr GGCCCTGCTGGTGGAGATA SEQ ID NO: 1161 ING1L NM_001564.1 FPr TGTTTCCAAGATCCTGCTGA SEQ ID NO: 1162 Probe CCATCTTTGCTTTATCTGAGGCTCGTTC SEQ ID NO: 1163 RPr TCTTTCTGGTTGGCTGGAAT SEQ ID NO: 1164 ING5 NM_032329.4 FPr CCTACAGCAAGTGCAAGGAA SEQ ID NO: 1165 Probe CCAGCTGCACTTTGTCGTCACTGT SEQ ID NO: 1166 RPr CATCTCGTAGGTCTGCATGG SEQ ID NO: 1167 INHA NM_002191.2 FPr CCTCCCAGTTTCATCTTCCACTA SEQ ID NO: 1168 Probe ATGTGCAGCCCACAACCACCATGA SEQ ID NO: 1169 RPr AGGGACTGGAAGGGACAGGTT SEQ ID NO: 1170 INHBA NM_002192.1 FPr GTGCCCGAGCCATATAGCA SEQ ID NO: 1171 Probe ACGTCCGGGTCCTCACTGTCCTTCC SEQ ID NO: 1172 RPr CGGTAGTGGTTGATGACTGTTGA SEQ ID NO: 1173 INHBB NM_002193.1 FPr AGCCTCCAGGATACCAGCAA SEQ ID NO: 1174 Probe AGCTAAGCTGCCATTTGTCACCG SEQ ID NO: 1175 RPr TCTCCGACTGACAGGCATTTG SEQ ID NO: 1176 IRS1 NM_005544.1 FPr CCACAGCTCACCTTCTGTCA SEQ ID NO: 1177 Probe TCCATCCCAGCTCCAGCCAG SEQ ID NO: 1178 RPr CCTCAGTGCCAGTCTCTTCC SEQ ID NO: 1179 ITGA3 NM_002204.1 FPr CCATGATCCTCACTCTGCTG SEQ ID NO: 1180 Probe CACTCCAGACCTCGCTTAGCATGG SEQ ID NO: 1181 RPr GAAGCTTTGTAGCCGGTGAT SEQ ID NO: 1182 ITGA4 NM_000885.2 FPr CAACGCTTCAGTGATCAATCC SEQ ID NO: 1183 Probe CGATCCTGCATCTGTAAATCGCCC SEQ ID NO: 1184 RPr GTCTGGCCGGGATTCTTT SEQ ID NO: 1185 ITGA5 NM_002205.1 FPr AGGCCAGCCCTACATTATCA SEQ ID NO: 1186 Probe TCTGAGCCTTGTCCTCTATCCGGC SEQ ID NO: 1187 RPr GTCTTCTCCACAGTCCAGCA SEQ ID NO: 1188 ITGA6 NM_000210.1 FPr CAGTGACAAACAGCCCTTCC SEQ ID NO: 1189 Probe TCGCCATCTTTTGTGGGATTCCTT SEQ ID NO: 1190 RPr GTTTAGCCTCATGGGCGTC SEQ ID NO: 1191 ITGA7 NM_002206.1 FPr GATATGATTGGTCGCTGCTTTG SEQ ID NO: 1192 Probe CAGCCAGGACCTGGCCATCCG SEQ ID NO: 1193 RPr AGAACTTCCATTCCCCACCAT SEQ ID NO: 1194 ITGAV NM_002210.2 FPr ACTCGGACTGCACAAGCTATT SEQ ID NO: 1195 Probe CCGACAGCCACAGAATAACCCAAA SEQ ID NO: 1196 RPr TGCCATCACCATTGAAATCT SEQ ID NO: 1197 ITGB1 NM_002211.2 FPr TCAGAATTGGATTTGGCTCA SEQ ID NO: 1198 Probe TGCTAATGTAAGGCATCACAGTCTTTTCCA SEQ ID NO: 1199 RPr CCTGAGCTTAGCTGGTGTTG SEQ ID NO: 1200 ITGB3 NM_000212.1 FPr ACCGGGAGCCCTACATGAC SEQ ID NO: 1201 Probe AAATACCTGCAACCGTTACTGCCGTGAC SEQ ID NO: 1202 RPr CCTTAAGCTCTTTCACTGACTCAATCT SEQ ID NO: 1203 ITGB4 NM_000213.2 FPr CAAGGTGCCCTCAGTGGA SEQ ID NO: 1204 Probe CACCAACCTGTACCCGTATTGCGA SEQ ID NO: 1205 RPr GCGCACACCTTCATCTCAT SEQ ID NO: 1206 ITGB5 NM_002213.3 FPr TCGTGAAAGATGACCAGGAG SEQ ID NO: 1207 Probe TGCTATGTTTCTACAAAACCGCCAAGG SEQ ID NO: 1208 RPr GGTGAACATCATGACGCAGT SEQ ID NO: 1209 K-ras NM_033360.2 FPr GTCAAAATGGGGAGGGACTA SEQ ID NO: 1210 Probe TGTATCTTGTTGAGCTATCCAAACTGCCC SEQ ID NO: 1211 RPr CAGGACCACCACAGAGTGAG SEQ ID NO: 1212 KCNH2 iso NM_000238.2 FPr GAGCGCAAAGTGGAAATCG SEQ ID NO: 1213 a/b Probe TAGGAAGCAGCTCCCATCTTTCCGGTA SEQ ID NO: 1214 RPr TCTTCACGGGCACCACATC SEQ ID NO: 1215 KCNH2 iso NM_172057.1 FPr TCCTGCTGCTGGTCATCTAC SEQ ID NO: 1216 a/c Probe TGTCTTCACACCCTACTCGGCTGC SEQ ID NO: 1217 RPr CCTTCTTCCGTCTCCTTCAG SEQ ID NO: 1218 KCNK4 NM_016611.2 FPr CCTATCAGCCGCTGGTGT SEQ ID NO: 1219 Probe ATCCTGCTCGGCCTGGCTTACTTC SEQ ID NO: 1220 RPr TGGTGGTGAGCACTGAGG SEQ ID NO: 1221 KDR NM_002253.1 FPr GAGGACGAAGGCCTCTACAC SEQ ID NO: 1222 Probe CAGGCATGCAGTGTTCTTGGCTGT SEQ ID NO: 1223 RPr AAAAATGCCTCCACTTTTGC SEQ ID NO: 1224 Ki-67 NM_002417.1 FPr CGGACTTTGGGTGCGACTT SEQ ID NO: 1225 Probe CCACTTGTCGAACCACCGCTCGT SEQ ID NO: 1226 RPr TTACAACTCTTCCACTGGGACGAT SEQ ID NO: 1227 KIAA0125 NM_014792.2 FPr GTGTCCTGGTCCATGTGGT SEQ ID NO: 1228 Probe CACGTGTCTCCACCTCCAAGGAGA SEQ ID NO: 1229 RPr GGGAGGTGCACACTGAGG SEQ ID NO: 1230 KIF22 NM_007317.1 FPr CTAAGGCACTTGCTGGAAGG SEQ ID NO: 1231 Probe TCCATAGGCAAGCACACTGGCATT SEQ ID NO: 1232 RPr TCTTCCCAGCTCCTGTGG SEQ ID NO: 1233 KIF2C NM_006845.2 FPr AATTCCTGCTCCAAAAGAAAGTCTT SEQ ID NO: 1234 Probe AAGCCGCTCCACTCGCATGTCC SEQ ID NO: 1235 RPr CGTGATGCGAAGCTCTGAGA SEQ ID NO: 1236 KIFC1 XM_371813.1 FPr CCACAGGGTTGAAGAACCAG SEQ ID NO: 1237 Probe AGCCAGTTCCTGCTGTTCCTGTCC SEQ ID NO: 1238 RPr CACCTGATGTGCCAGACTTC SEQ ID NO: 1239 Kitlng NM_000899.1 FPr GTCCCCGGGATGGATGTT SEQ ID NO: 1240 Probe CATCTCGCTTATCCAACAATGACTTGGCA SEQ ID NO: 1241 RPr GATCAGTCAAGCTGTCTGACAATTG SEQ ID NO: 1242 KLF5 NM_001730.3 FPr GTGCAACCGCAGCTTCTC SEQ ID NO: 1243 Probe CTCTGACCACCTGGCCCTGCATAT SEQ ID NO: 1244 RPr CGGGCAGTGCTCAGTTCT SEQ ID NO: 1245 KLF6 NM_001300.4 FPr CACGAGACCGGCTACTTCTC SEQ ID NO: 1246 Probe AGTACTCCTCCAGAGACGGCAGCG SEQ ID NO: 1247 RPr GCTCTAGGCAGGTCTGTTGC SEQ ID NO: 1248 KLK10 NM_002776.1 FPr GCCCAGAGGCTCCATCGT SEQ ID NO: 1249 Probe CCTCTTCCTCCCCAGTCGGCTGA SEQ ID NO: 1250 RPr CAGAGGTTTGAACAGTGCAGACA SEQ ID NO: 1251 KLK6 NM_002774.2 FPr GACGTGAGGGTCCTGATTCT SEQ ID NO: 1252 Probe TTACCCCAGCTCCATCCTTGCATC SEQ ID NO: 1253 RPr TCCTCACTCATCACGTCCTC SEQ ID NO: 1254 KLRK1 NM_007360.1 FPr TGAGAGCCAGGCTTCTTGTA SEQ ID NO: 1255 Probe TGTCTCAAAATGCCAGCCTTCTGAA SEQ ID NO: 1256 RPr ATCCTGGTCCTCTTTGCTGT SEQ ID NO: 1257 KNTC2 NM_006101.1 FPr ATGTGCCAGTGAGCTTGAGT SEQ ID NO: 1258 Probe CCTTGGAGAAACACAAGCACCTGC SEQ ID NO: 1259 RPr TGAGCCCCTGGTTAACAGTA SEQ ID NO: 1260 KRAS2 NM_004985.3 FPr GAGACCAAGGTTGCAAGGC SEQ ID NO: 1261 Probe AAGCTCAAAGGTTCACACAGGGCC SEQ ID NO: 1262 RPr CAGTCCATGCTGTGAAACTCTC SEQ ID NO: 1263 KRT19 NM_002276.1 FPr TGAGCGGCAGAATCAGGAGTA SEQ ID NO: 1264 Probe CTCATGGACATCAAGTCGCGGCTG SEQ ID NO: 1265 RPr TGCGGTAGGTGGCAATCTC SEQ ID NO: 1266 KRT8 NM_002273.1 FPr GGATGAAGCTTACATGAACAAGGTAGA SEQ ID NO: 1267 Probe CGTCGGTCAGCCCTTCCAGGC SEQ ID NO: 1268 RPr CATATAGCTGCCTGAGGAAGTTGAT SEQ ID NO: 1269 LAMA3 NM_000227.2 FPr CAGATGAGGCACATGGAGAC SEQ ID NO: 1270 Probe CTGATTCCTCAGGTCCTTGGCCTG SEQ ID NO: 1271 RPr TTGAAATGGCAGAACGGTAG SEQ ID NO: 1272 LAMB3 NM_000228.1 FPr ACTGACCAAGCCTGAGACCT SEQ ID NO: 1273 Probe CCACTCGCCATACTGGGTGCAGT SEQ ID NO: 1274 RPr GTCACACTTGCAGCATTTCA SEQ ID NO: 1275 LAMC2 NM_005562.1 FPr ACTCAAGCGGAAATTGAAGCA SEQ ID NO: 1276 Probe AGGTCTTATCAGCACAGTCTCCGCCTCC SEQ ID NO: 1277 RPr ACTCCCTGAAGCCGAGACACT SEQ ID NO: 1278 LAT NM_014387.2 FPr GTGAACGTTCCGGAGAGC SEQ ID NO: 1279 Probe ATCCAGAGACGCTTCTGCGCTCTC SEQ ID NO: 1280 RPr ACATTCACATACTCCCGGCT SEQ ID NO: 1281 LCN2 NM_005564.2 FPr CGCTGGGCAACATTAAGAG SEQ ID NO: 1282 Probe TCACCACTCGGACGAGGTAACTCG SEQ ID NO: 1283 RPr AGCATGCTGGTTGTAGTTGGT SEQ ID NO: 1284 LDLRAP1 NM_015627.1 FPr CAGTGCCTCTCGCCTGTC SEQ ID NO: 1285 Probe ACTGGGACAAGCCTGACAGCAGC SEQ ID NO: 1286 RPr TGAAGAGGTCATCCTGCTCTG SEQ ID NO: 1287 LEF NM_016269.2 FPr GATGACGGAAAGCATCCAG SEQ ID NO: 1288 Probe TGGAGGCCTCTACAACAAGGGACC SEQ ID NO: 1289 RPr CCCGGAATAACTCGAGTAGGA SEQ ID NO: 1290 LGALS3 NM_002306.1 FPr AGCGGAAAATGGCAGACAAT SEQ ID NO: 1291 Probe ACCCAGATAACGCATCATGGAGCGA SEQ ID NO: 1292 RPr CTTGAGGGTTTGGGTTTCCA SEQ ID NO: 1293 LGMN NM_001008530.1 FPr TTGGTGCCGTTCCTATAGATG SEQ ID NO: 1294 Probe CAGTGCTTGCCTCCATCTTCAGGA SEQ ID NO: 1295 RPr GAACCTGCCACGATCACC SEQ ID NO: 1296 LILRB3 NM_006864.1 FPr CACCTGGTCTGGGAAGATACC SEQ ID NO: 1297 Probe ACCGAGACCCCAATCAAAACCTCC SEQ ID NO: 1298 RPr AAGAGCAGCAGGACGAAGG SEQ ID NO: 1299 LMNB1 NM_005573.1 FPr TGCAAACGCTGGTGTCACA SEQ ID NO: 1300 Probe CAGCCCCCCAACTGACCTCATC SEQ ID NO: 1301 RPr CCCCACGAGTTCTGGTTCTTC SEQ ID NO: 1302 LMYC NM_012421.1 FPr CCCATCCAGAACACTGATTG SEQ ID NO: 1303 Probe TGACCTCCATCCCTTTCACTTGAATG SEQ ID NO: 1304 RPr CTGCTTTCTATGCACCCTTTC SEQ ID NO: 1305 LOX NM_002317.3 FPr CCAATGGGAGAACAACGG SEQ ID NO: 1306 Probe CAGGCTCAGCAAGCTGAACACCTG SEQ ID NO: 1307 RPr CGCTGAGGCTGGTACTGTG SEQ ID NO: 1308 LOXL2 NM_002318.1 FPr TCAGCGGGCTCTTAAACAA SEQ ID NO: 1309 Probe CAGCTGTCCCCGCAGTAAAGAAGC SEQ ID NO: 1310 RPr AAGACAGGAGTTGACCACGC SEQ ID NO: 1311 LRP5 NM_002335.1 FPr CGACTATGACCCACTGGACA SEQ ID NO: 1312 Probe CGCCCATCCACCCAGTAGATGAAC SEQ ID NO: 1313 RPr CTTGGCTCGCTTGATGTTC SEQ ID NO: 1314 LRP6 NM_002336.1 FPr GGATGTAGCCATCTCTGCCT SEQ ID NO: 1315 Probe ATAGACCTCAGGGCCTTCGCTGTG SEQ ID NO: 1316 RPr AGTTCAAAGCCAATAGGGCA SEQ ID NO: 1317 LY6D NM_003695.2 FPr AATGCTGATGACTTGGAGCAG SEQ ID NO: 1318 Probe CACAGACCCCACAGAGGATGAAGC SEQ ID NO: 1319 RPr CTGCATCCTCTGTGGGGT SEQ ID NO: 1320 MAD NM_002357.1 FPr TGGTTCTGATTAGGTAACGTATTGGA SEQ ID NO: 1321 Probe CTGCCCACAACTCCCTTGCACGTAA SEQ ID NO: 1322 RPr GGTCAAGGTGGGACACTGAAG SEQ ID NO: 1323 MAD1L1 NM_003550.1 FPr AGAAGCTGTCCCTGCAAGAG SEQ ID NO: 1324 Probe CATGTTCTTCACAATCGCTGCATCC SEQ ID NO: 1325 RPr AGCCGTACCAGCTCAGACTT SEQ ID NO: 1326 MAD2L1 NM_002358.2 FPr CCGGGAGCAGGGAATCAC SEQ ID NO: 1327 Probe CGGCCACGATTTCGGCGCT SEQ ID NO: 1328 RPr ATGCTGTTGATGCCGAATGA SEQ ID NO: 1329 MADH2 NM_005901.2 FPr GCTGCCTTTGGTAAGAACATGTC SEQ ID NO: 1330 Probe TCCATCTTGCCATTCACGCCGC SEQ ID NO: 1331 RPr ATCCCAGCAGTCTCTTCACAACT SEQ ID NO: 1332 MADH4 NM_005359.3 FPr GGACATTACTGGCCTGTTCACA SEQ ID NO: 1333 Probe TGCATTCCAGCCTCCCATTTCCA SEQ ID NO: 1334 RPr ACCAATACTCAGGAGCAGGATGA SEQ ID NO: 1335 MADH7 NM_005904.1 FPr TCCATCAAGGCTTTCGACTA SEQ ID NO: 1336 Probe CTGCAGGCTGTACGCCTTCTCG SEQ ID NO: 1337 RPr CTGCTGCATAAACTCGTGGT SEQ ID NO: 1338 MAP2 NM_031846.1 FPr CGGACCACCAGGTCAGAG SEQ ID NO: 1339 Probe CCACTCTTCCCTGCTCTGCGAATT SEQ ID NO: 1340 RPr CAGGGGTAGTGGGTGTTGAG SEQ ID NO: 1341 MAP2K1 NM_002755.2 FPr GCCTTTCTTACCCAGAAGCAGAA SEQ ID NO: 1342 Probe TCTCAAAGTCGTCATCCTTCAGTTCTCCCA SEQ ID NO: 1343 RPr CAGCCCCCAGCTCACTGAT SEQ ID NO: 1344 MAP3K1 XM_042066.8 FPr GGTTGGCATCAAAAGGAACT SEQ ID NO: 1345 Probe AATTGTCCCTGAAACTCTCCTGCACC SEQ ID NO: 1346 RPr TGCCATAAATGCAATTGTCC SEQ ID NO: 1347 MAPK14 NM_139012.1 FPr TGAGTGGAAAAGCCTGACCTATG SEQ ID NO: 1348 Probe TGAAGTCATCAGCTTTGTGCCACCACC SEQ ID NO: 1349 RPr GGACTCCATCTCTTCTTGGTCAA SEQ ID NO: 1350 Maspin NM_002639.1 FPr CAGATGGCCACTTTGAGAACATT SEQ ID NO: 1351 Probe AGCTGACAACAGTGTGAACGACCAGACC SEQ ID NO: 1352 RPr GGCAGCATTAACCACAAGGATT SEQ ID NO: 1353 MAX NM_002382.3 FPr CAAACGGGCTCATCATAATGC SEQ ID NO: 1354 Probe TGATGTGGTCCCTACGTTTTCGTTCCA SEQ ID NO: 1355 RPr TCCCGCAAACTGTGAAAGCT SEQ ID NO: 1356 MCM2 NM_004526.1 FPr GACTTTTGCCCGCTACCTTTC SEQ ID NO: 1357 Probe ACAGCTCATTGTTGTCACGCCGGA SEQ ID NO: 1358 RPr GCCACTAACTGCTTCAGTATGAAGAG SEQ ID NO: 1359 MCM3 NM_002388.2 FPr GGAGAACAATCCCCTTGAGA SEQ ID NO: 1360 Probe TGGCCTTTCTGTCTACAAGGATCACCA SEQ ID NO: 1361 RPr ATCTCCTGGATGGTGATGGT SEQ ID NO: 1362 MCM6 NM_005915.2 FPr TGATGGTCCTATGTGTCACATTCA SEQ ID NO: 1363 Probe CAGGTTTCATACCAACACAGGCTTCAGC SEQ ID NO: 1364 AC RPr TGGGACAGGAAACACACCAA SEQ ID NO: 1365 MCP1 NM_002982.1 FPr CGCTCAGCCAGATGCAATC SEQ ID NO: 1366 Probe TGCCCCAGTCACCTGCTGTTA SEQ ID NO: 1367 RPr GCACTGAGATCTTCCTATTGGTGAA SEQ ID NO: 1368 MDK NM_002391.2 FPr GGAGCCGACTGCAAGTACA SEQ ID NO: 1369 Probe ATCACACGCACCCCAGTTCTCAAA SEQ ID NO: 1370 RPr GACTTTGGTGCCTGTGCC SEQ ID NO: 1371 MDM2 NM_002392.1 FPr CTACAGGGACGCCATCGAA SEQ ID NO: 1372 Probe CTTACACCAGCATCAAGATCCGG SEQ ID NO: 1373 RPr ATCCAACCAATCACCTGAATGTT SEQ ID NO: 1374 MGAT5 NM_002410.2 FPr GGAGTCGAAGGTGGACAATC SEQ ID NO: 1375 Probe AATGGCACCGGAACAAACTCAACC SEQ ID NO: 1376 RPr TGGGAACAGCTGTAGTGGAGT SEQ ID NO: 1377 MGMT NM_002412.1 FPr GTGAAATGAAACGCACCACA SEQ ID NO: 1378 Probe CAGCCCTTTGGGGAAGCTGG SEQ ID NO: 1379 RPr GACCCTGCTCACAACCAGAC SEQ ID NO: 1380 mGST1 NM_020300.2 FPr ACGGATCTACCACACCATTGC SEQ ID NO: 1381 Probe TTTGACACCCCTTCCCCAGCCA SEQ ID NO: 1382 RPr TCCATATCCAACAAAAAAACTCAAAG SEQ ID NO: 1383 MMP1 NM_002421.2 FPr GGGAGATCATCGGGACAACTC SEQ ID NO: 1384 Probe AGCAAGATTTCCTCCAGGTCCATCAAAA SEQ ID NO: 1385 GG RPr GGGCCTGGTTGAAAAGCAT SEQ ID NO: 1386 MMP12 NM_002426.1 FPr CCAACGCTTGCCAAATCCT SEQ ID NO: 1387 Probe AACCAGCTCTCTGTGACCCCAATT SEQ ID NO: 1388 RPr ACGGTAGTGACAGCATCAAAACTC SEQ ID NO: 1389 MMP2 NM_004530.1 FPr CCATGATGGAGAGGCAGACA SEQ ID NO: 1390 Probe CTGGGAGCATGGCGATGGATACCC SEQ ID NO: 1391 RPr GGAGTCCGTCCTTACCGTCAA SEQ ID NO: 1392 MMP7 NM_002423.2 FPr GGATGGTAGCAGTCTAGGGATTAACT SEQ ID NO: 1393 Probe CCTGTATGCTGCAACTCATGAACTTGGC SEQ ID NO: 1394 RPr GGAATGTCCCATACCCAAAGAA SEQ ID NO: 1395 MMP9 NM_004994.1 FPr GAGAACCAATCTCACCGACA SEQ ID NO: 1396 Probe ACAGGTATTCCTCTGCCAGCTGCC SEQ ID NO: 1397 RPr CACCCGAGTGTAACCATAGC SEQ ID NO: 1398 MRP1 NM_004996.2 FPr TCATGGTGCCCGTCAATG SEQ ID NO: 1399 Probe ACCTGATACGTCTTGGTCTTCATCGCCAT SEQ ID NO: 1400 RPr CGATTGTCTTTGCTCTTCATGTG SEQ ID NO: 1401 MRP2 NM_000392.1 FPr AGGGGATGACTTGGACACAT SEQ ID NO: 1402 Probe CTGCCATTCGACATGACTGCAATTT SEQ ID NO: 1403 RPr AAAACTGCATGGCTTTGTCA SEQ ID NO: 1404 MRP3 NM_003786.2 FPr TCATCCTGGCGATCTACTTCCT SEQ ID NO: 1405 Probe TCTGTCCTGGCTGGAGTCGCTTTCAT SEQ ID NO: 1406 RPr CCGTTGAGTGGAATCAGCAA SEQ ID NO: 1407 MRP4 NM_005845.1 FPr AGCGCCTGGAATCTACAACT SEQ ID NO: 1408 Probe CGGAGTCCAGTGTTTTCCCACTTG SEQ ID NO: 1409 RPr AGAGCCCCTGGAGAGAAGAT SEQ ID NO: 1410 MRPL40 NM_003776.2 FPr ACTTGCAGGCTGCTATCCTT SEQ ID NO: 1411 Probe TTCCTACTCTCAGGGGCAGCATGTT SEQ ID NO: 1412 RPr AGCAGACTTGAACCCTGGTC SEQ ID NO: 1413 MSH2 NM_000251.1 FPr GATGCAGAATTGAGGCAGAC SEQ ID NO: 1414 Probe CAAGAAGATTTACTTCGTCGATTCCCAGA SEQ ID NO: 1415 RPr TCTTGGCAAGTCGGTTAAGA SEQ ID NO: 1416 MSH3 NM_002439.1 FPr TGATTACCATCATGGCTCAGA SEQ ID NO: 1417 Probe TCCCAATTGTCGCTTCTTCTGCAG SEQ ID NO: 1418 RPr CTTGTGAAAATGCCATCCAC SEQ ID NO: 1419 MSH6 NM_000179.1 FPr TCTATTGGGGGATTGGTAGG SEQ ID NO: 1420 Probe CCGTTACCAGCTGGAAATTCCTGAGA SEQ ID NO: 1421 RPr CAAATTGCGAGTGGTGAAAT SEQ ID NO: 1422 MT3 NM_005954.1 FPr GTGTGAGAAGTGTGCCAAGG SEQ ID NO: 1423 Probe CTCTCCGCCTTTGCACACACAGT SEQ ID NO: 1424 RPr CTGCACTTCTCTGCTTCTGC SEQ ID NO: 1425 MTA1 NM_004689.2 FPr CCGCCCTCACCTGAAGAGA SEQ ID NO: 1426 Probe CCCAGTGTCCGCCAAGGAGCG SEQ ID NO: 1427 RPr GGAATAAGTTAGCCGCGCTTCT SEQ ID NO: 1428 MUC1 NM_002456.1 FPr GGCCAGGATCTGTGGTGGTA SEQ ID NO: 1429 Probe CTCTGGCCTTCCGAGAAGGTACC SEQ ID NO: 1430 RPr CTCCACGTCGTGGACATTGA SEQ ID NO: 1431 MUC2 NM_002457.1 FPr CTATGAGCCATGTGGGAACC SEQ ID NO: 1432 Probe AGCTTCGAGACCTGCAGGACCATC SEQ ID NO: 1433 RPr ATGTTGGAGTGGATGCCG SEQ ID NO: 1434 MUC5B XM_039877.11 FPr TGCCCTTGCACTGTCCTAA SEQ ID NO: 1435 Probe TCAGCCATCCTGCACACCTACACC SEQ ID NO: 1436 RPr CAGCCACACTCATCCACG SEQ ID NO: 1437 MUTYH NM_012222.1 FPr GTACGACCAAGAGAAACGGG SEQ ID NO: 1438 Probe TCTGCCCGTCTTCTCCATGGTAGG SEQ ID NO: 1439 RPr CCTGTCCAGGTCCATCTCA SEQ ID NO: 1440 MVP NM_017458.1 FPr ACGAGAACGAGGGCATCTATGT SEQ ID NO: 1441 Probe CGCACCTTTCCGGTCTTGACATCCT SEQ ID NO: 1442 RPr GCATGTAGGTGCTTCCAATCAC SEQ ID NO: 1443 MX1 NM_002462.2 FPr GAAGGAATGGGAATCAGTCATGA SEQ ID NO: 1444 Probe TCACCCTGGAGATCAGCTCCCGA SEQ ID NO: 1445 RPr GTCTATTAGAGTCAGATCCGGGACAT SEQ ID NO: 1446 MXD4 NM_006454.2 FPr AGAAACTGGAGGAGCAGGAC SEQ ID NO: 1447 Probe TGCAGCTGCTCCTTGATGCTCAGT SEQ ID NO: 1448 RPr CTTCAGGAAACGATGCTCCT SEQ ID NO: 1449 MYBL2 NM_002466.1 FPr GCCGAGATCGCCAAGATG SEQ ID NO: 1450 Probe CAGCATTGTCTGTCCTCCCTGGCA SEQ ID NO: 1451 RPr CTTTTGATGGTAGAGTTCCAGTGATTC SEQ ID NO: 1452 MYH11 NM_002474.1 FPr CGGTACTTCTCAGGGCTAATATATACG SEQ ID NO: 1453 Probe CTCTTCTGCGTGGTGGTCAACCCCTA SEQ ID NO: 1454 RPr CCGAGTAGATGGGCAGGTGTT SEQ ID NO: 1455 MYLK NM_053025.1 FPr TGACGGAGCGTGAGTGCAT SEQ ID NO: 1456 Probe CCCTCCGAGATCTGCCGCATGTACT SEQ ID NO: 1457 RPr ATGCCCTGCTTGTGGATGTAC SEQ ID NO: 1458 NAT2 NM_000015.1 FPr TAACTGACATTCTTGAGCACCAGAT SEQ ID NO: 1459 Probe CGGGCTGTTCCCTTTGAGAACCTTAACA SEQ ID NO: 1460 RPr ATGGCTTGCCCACAATGC SEQ ID NO: 1461 NAV2 NM_182964.3 FPr CTCTCCCAGCACAGCTTGA SEQ ID NO: 1462 Probe CCTCACTGAGTCAACCAGCCTGGA SEQ ID NO: 1463 RPr CACCAGTGTCATCCAGCAAC SEQ ID NO: 1464 NCAM1 NM_000615.1 FPr TAGTTCCCAGCTGACCATCA SEQ ID NO: 1465 Probe CTCAGCCTCGTCGTTCTTATCCACC SEQ ID NO: 1466 RPr CAGCCTTGTTCTCAGCAATG SEQ ID NO: 1467 NDE1 NM_017668.1 FPr CTACTGCGGAAAGTCGGG SEQ ID NO: 1468 Probe CTGGAGTCCAAACTCGCTTCCTGC SEQ ID NO: 1469 RPr GGACTGATCGTACACGAGGTT SEQ ID NO: 1470 NDRG1 NM_006096.2 FPr AGGGCAACATTCCACAGC SEQ ID NO: 1471 Probe CTGCAAGGACACTCATCACAGCCA SEQ ID NO: 1472 RPr CAGTGCTCCTACTCCGGC SEQ ID NO: 1473 NDUFS3 NM_004551.1 FPr TATCCATCCTGATGGCGTC SEQ ID NO: 1474 Probe CCCAGTGCTGACTTTCCTCAGGGA SEQ ID NO: 1475 RPr TTGAACTGTGCATTGGTGTG SEQ ID NO: 1476 NEDD8 NM_006156.1 FPr TGCTGGCTACTGGGTGTTAGT SEQ ID NO: 1477 Probe TGCAGTCCTGTGTGCTTCCCTCTC SEQ ID NO: 1478 RPr GACAACCAGGGACACAGTCA SEQ ID NO: 1479 NEK2 NM_002497.1 FPr GTGAGGCAGCGCGACTCT SEQ ID NO: 1480 Probe TGCCTTCCCGGGCTGAGGACT SEQ ID NO: 1481 RPr TGCCAATGGTGTACAACACTTCA SEQ ID NO: 1482 NF2 NM_000268.2 FPr ACTCCAGAGCTGACCTCCAC SEQ ID NO: 1483 Probe CTACAATGACTTCCCAGGCTGGGC SEQ ID NO: 1484 RPr TCAGGGCTTCAGTGTCTCAC SEQ ID NO: 1485 NFKBp50 NM_003998.1 FPr CAGACCAAGGAGATGGACCT SEQ ID NO: 1486 Probe AAGCTGTAAACATGAGCCGCACCA SEQ ID NO: 1487 RPr AGCTGCCAGTGCTATCCG SEQ ID NO: 1488 NFKBp65 NM_021975.1 FPr CTGCCGGGATGGCTTCTAT SEQ ID NO: 1489 Probe CTGAGCTCTGCCCGGACCGCT SEQ ID NO: 1490 RPr CCAGGTTCTGGAAACTGTGGAT SEQ ID NO: 1491 NISCH NM_007184.1 FPr CCAAGGAATCATGTTCGTTCAG SEQ ID NO: 1492 Probe TGGCCAGCAGCCTCTCGTCCAC SEQ ID NO: 1493 RPr TGGTGCTCGGGAGTCAGACT SEQ ID NO: 1494 Nkd-1 NM_033119.3 FPr GAGAGAGTGAGCGAACCCTG SEQ ID NO: 1495 Probe CCAGGCTCCAAGAAGCAGCTGAAG SEQ ID NO: 1496 RPr CGTCGCACTGGAGCTCTT SEQ ID NO: 1497 NMB NM_021077.1 FPr GGCTGCTGGTACAAATACTGC SEQ ID NO: 1498 Probe TGTCTGCCCCTATTATTGGTGTCATTTCT SEQ ID NO: 1499 RPr CAATCTAAGCCACGCTGTTG SEQ ID NO: 1500 NMBR NM_002511.1 FPr TGATCCATCTCTAGGCCACA SEQ ID NO: 1501 Probe TTGTCACCTTAGTTGCCCGGGTTC SEQ ID NO: 1502 RPr GAGCAAATGGGTTGACACAA SEQ ID NO: 1503 NME1 NM_000269.1 FPr CCAACCCTGCAGACTCCAA SEQ ID NO: 1504 Probe CCTGGGACCATCCGTGGAGACTTCT SEQ ID NO: 1505 RPr ATGTATAATGTTCCTGCCAACTTGTATG SEQ ID NO: 1506 NOS3 NM_000603.2 FPr ATCTCCGCCTCGCTCATG SEQ ID NO: 1507 Probe TTCACTCGCTTCGCCATCACCG SEQ ID NO: 1508 RPr TCGGAGCCATACAGGATTGTC SEQ ID NO: 1509 NOTCH1 NM_017617.2 FPr CGGGTCCACCAGTTTGAATG SEQ ID NO: 1510 Probe CCGCTCTGCAGCCGGGACA SEQ ID NO: 1511 RPr GTTGTATTGGTTCGGCACCAT SEQ ID NO: 1512 NOTCH2 NM_024408.2 FPr CACTTCCCTGCTGGGATTAT SEQ ID NO: 1513 Probe CCGTGTTGCACAGCTCATCACACT SEQ ID NO: 1514 RPr AGTTGTCAAACAGGCACTCG SEQ ID NO: 1515 NPM1 NM_002520.2 FPr AATGTTGTCCAGGTTCTATTGC SEQ ID NO: 1516 Probe AACAGGCATTTTGGACAACACATTCTTG SEQ ID NO: 1517 RPr CAAGCAAAGGGTGGAGTTC SEQ ID NO: 1518 NR4A1 NM_002135.2 FPr CACAGCTTGCTTGTCGATGTC SEQ ID NO: 1519 Probe CCTTCGCCTGCCTCTCTGCCC SEQ ID NO: 1520 RPr ATGCCGGTCGGTGATGAG SEQ ID NO: 1521 NRG1 NM_013957.1 FPr CGAGACTCTCCTCATAGTGAAAGGTAT SEQ ID NO: 1522 Probe ATGACCACCCCGGCTCGTATGTCA SEQ ID NO: 1523 RPr CTTGGCGTGTGGAAATCTACAG SEQ ID NO: 1524 NRP1 NM_003873.1 FPr CAGCTCTCTCCACGCGATTC SEQ ID NO: 1525 Probe CAGGATCTACCCCGAGAGAGCCACTCAT SEQ ID NO: 1526 RPr CCCAGCAGCTCCATTCTGA SEQ ID NO: 1527 NRP2 NM_003872.1 FPr CTACAGCCTAAACGGCAAGG SEQ ID NO: 1528 Probe AGGACCCCAGGACCCAGCAG SEQ ID NO: 1529 RPr GTTCCCTTCGAACAGCTTTG SEQ ID NO: 1530 NTN1 NM_004822.1 FPr AGAAGGACTATGCCGTCCAG SEQ ID NO: 1531 Probe ATCCACATCCTGAAGGCGGACAAG SEQ ID NO: 1532 RPr CCGTGAACTTCCACCAGTC SEQ ID NO: 1533 NUFIP1 NM_012345.1 FPr GCTTCCACATCGTGGTATTG SEQ ID NO: 1534 Probe CTTCTGATAGGTTTCCTCGGCATCAGA SEQ ID NO: 1535 RPr AACTGCAGGGTTGAAGGACT SEQ ID NO: 1536 ODC1 NM_002539.1 FPr AGAGATCACCGGCGTAATCAA SEQ ID NO: 1537 Probe CCAGCGTTGGACAAATACTTTCCGTCA SEQ ID NO: 1538 RPr CGGGCTCAGCTATGATTCTCA SEQ ID NO: 1539 OPN, NM_000582.1 FPr CAACCGAAGTTTTCACTCCAGTT SEQ ID NO: 1540 osteopontin Probe TCCCCACAGTAGACACATATGATGGCCG SEQ ID NO: 1541 RPr CCTCAGTCCATAAACCACACTATCA SEQ ID NO: 1542 ORC1L NM_004153.2 FPr TCCTTGACCATACCGGAGG SEQ ID NO: 1543 Probe TGCATGTACATCTCCGGTGTCCCT SEQ ID NO: 1544 RPr CAGTGGCAGTCTTCCCTGTC SEQ ID NO: 1545 OSM NM_020530.3 FPr GTTTCTGAAGGGGAGGTCAC SEQ ID NO: 1546 Probe CTGAGCTGGCCTCCTATGCCTCAT SEQ ID NO: 1547 RPr AGGTGTCTGGTTTGGGACA SEQ ID NO: 1548 OSMR NM_003999.1 FPr GCTCATCATGGTCATGTGCT SEQ ID NO: 1549 Probe CAGGTCTCCTTGATCCACTGACTTTTCA SEQ ID NO: 1550 RPr TGTAAGGGTCAGGGATGTCA SEQ ID NO: 1551 P14ARF S78535.1 FPr CCCTCGTGCTGATGCTACT SEQ ID NO: 1552 Probe CTGCCCTAGACGCTGGCTCCTC SEQ ID NO: 1553 RPr CATCATGACCTGGTCTTCTAGG SEQ ID NO: 1554 p16-INK4 L27211.1 FPr GCGGAAGGTCCCTCAGACA SEQ ID NO: 1555 Probe CTCAGAGCCTCTCTGGTTCTTTCAATCGG SEQ ID NO: 1556 RPr TGATGATCTAAGTTTCCCGAGGTT SEQ ID NO: 1557 p21 NM_000389.1 FPr TGGAGACTCTCAGGGTCGAAA SEQ ID NO: 1558 Probe CGGCGGCAGACCAGCATGAC SEQ ID NO: 1559 RPr GGCGTTTGGAGTGGTAGAAATC SEQ ID NO: 1560 p27 NM_004064.1 FPr CGGTGGACCACGAAGAGTTAA SEQ ID NO: 1561 Probe CCGGGACTTGGAGAAGCACTGCA SEQ ID NO: 1562 RPr GGCTCGCCTCTTCCATGTC SEQ ID NO: 1563 P53 NM_000546.2 FPr CTTTGAACCCTTGCTTGCAA SEQ ID NO: 1564 Probe AAGTCCTGGGTGCTTCTGACGCACA SEQ ID NO: 1565 RPr CCCGGGACAAAGCAAATG SEQ ID NO: 1566 p53R2 AB036063.1 FPr CCCAGCTAGTGTTCCTCAGA SEQ ID NO: 1567 Probe TCGGCCAGCTTTTTCCAATCTTTG SEQ ID NO: 1568 RPr CCGTAAGCCCTTCCTCTATG SEQ ID NO: 1569 PADI4 NM_012387.1 FPr AGCAGTGGCTTGCTTTCTTC SEQ ID NO: 1570 Probe CCTGTGATGTCCCAGTTTCCCACTC SEQ ID NO: 1571 RPr TGCTAGGACCATGTTGGGAT SEQ ID NO: 1572 PAI1 NM_000602.1 FPr CCGCAACGTGGTTTTCTCA SEQ ID NO: 1573 Probe CTCGGTGTTGGCCATGCTCCAG SEQ ID NO: 1574 RPr TGCTGGGTTTCTCCTCCTGTT SEQ ID NO: 1575 Pak1 NM_002576.3 FPr GAGCTGTGGGTTGTTATGGA SEQ ID NO: 1576 Probe ACATCTGTCAAGGAGCCTCCAGCC SEQ ID NO: 1577 RPr CCATGCAAGTTTCTGTCACC SEQ ID NO: 1578 PARC NM_015089.1 FPr GGAGCTGACCTGCTTCCTAC SEQ ID NO: 1579 Probe TCCTTATGCATCGAGGCCAGGC SEQ ID NO: 1580 RPr AGCAGAGCACCACAGCATAG SEQ ID NO: 1581 PCAF NM_003884.3 FPr AGGTGGCTGTGTTACTGCAA SEQ ID NO: 1582 Probe TGCCACAGTTCTGCGACAGTCTACC SEQ ID NO: 1583 RPr CACCTGTGTGGTTTCGTACC SEQ ID NO: 1584 PCNA NM_002592.1 FPr GAAGGTGTTGGAGGCACTCAAG SEQ ID NO: 1585 Probe ATCCCAGCAGGCCTCGTTGATGAG SEQ ID NO: 1586 RPr GGTTTACACCGCTGGAGCTAA SEQ ID NO: 1587 PDGFA NM_002607.2 FPr TTGTTGGTGTGCCCTGGTG SEQ ID NO: 1588 Probe TGGTGGCGGTCACTCCCTCTGC SEQ ID NO: 1589 RPr TGGGTTCTGTCCAAACACTGG SEQ ID NO: 1590 PDGFB NM_002608.1 FPr ACTGAAGGAGACCCTTGGAG SEQ ID NO: 1591 Probe TCTCCTGCCGATGCCCCTAGG SEQ ID NO: 1592 RPr TAAATAACCCTGCCCACACA SEQ ID NO: 1593 PDGFC NM_016205.1 FPr AGTTACTAAAAAATACCACGAGGTCCTT SEQ ID NO: 1594 Probe CCCTGACACCGGTCTTTGGTCTCAACT SEQ ID NO: 1595 RPr GTCGGTGAGTGATTTGTGCAA SEQ ID NO: 1596 PDGFD NM_025208.2 FPr TATCGAGGCAGGTCATACCA SEQ ID NO: 1597 Probe TCCAGGTCAACTTTTGACTTCCGGT SEQ ID NO: 1598 RPr TAACGCTTGGCATCATCATT SEQ ID NO: 1599 PDGFRa NM_006206.2 FPr GGGAGTTTCCAAGAGATGGA SEQ ID NO: 1600 Probe CCCAAGACCCGACCAAGCACTAG SEQ ID NO: 1601 RPr CTTCAACCACCTTCCCAAAC SEQ ID NO: 1602 PDGFRb NM_002609.2 FPr CCAGCTCTCCTTCCAGCTAC SEQ ID NO: 1603 Probe ATCAATGTCCCTGTCCGAGTGCTG SEQ ID NO: 1604 RPr GGGTGGCTCTCACTTAGCTC SEQ ID NO: 1605 PFN1 NM_005022.2 FPr GGAAAACGTTCGTCAACATC SEQ ID NO: 1606 Probe CAACCAGGACACCCACCTCAGCT SEQ ID NO: 1607 RPr AAAACTTGACCGGTCTTTGC SEQ ID NO: 1608 PFN2 NM_053024.1 FPr TCTATACGTCGATGGTGACTGC SEQ ID NO: 1609 Probe CTCCCCACCTTGACTCTTTGTCCG SEQ ID NO: 1610 RPr GCCGACAGCCACATTGTAT SEQ ID NO: 1611 PGK1 NM_000291.1 FPr AGAGCCAGTTGCTGTAGAACTCAA SEQ ID NO: 1612 Probe TCTCTGCTGGGCAAGGATGTTCTGTTC SEQ ID NO: 1613 RPr CTGGGCCTACACAGTCCTTCA SEQ ID NO: 1614 PI3K NM_002646.2 FPr TGCTACCTGGACAGCCCG SEQ ID NO: 1615 Probe TCCTCCTGAAACGAGCTGTGTCTGACTT SEQ ID NO: 1616 RPr AGGCCGTCCTTCAGTAACCA SEQ ID NO: 1617 PI3KC2A NM_002645.1 FPr ATACCAATCACCGCACAAACC SEQ ID NO: 1618 Probe TGCGCTGTGACTGGACTTAACAAATAGC SEQ ID NO: 1619 CT RPr CACACTAGCATTTTCTCCGCATA SEQ ID NO: 1620 PIK3CA NM_006218.1 FPr GTGATTGAAGAGCATGCCAA SEQ ID NO: 1621 Probe TCCTGCTTCTCGGGATACAGACCA SEQ ID NO: 1622 RPr GTCCTGCGTGGGAATAGC SEQ ID NO: 1623 PIM1 NM_002648.2 FPr CTGCTCAAGGACACCGTCTA SEQ ID NO: 1624 Probe TACACTCGGGTCCCATCGAAGTCC SEQ ID NO: 1625 RPr GGATCCACTCTGGAGGGC SEQ ID NO: 1626 Pin1 NM_006221.1 FPr GATCAACGGCTACATCCAGA SEQ ID NO: 1627 Probe TCAAAGTCCTCCTCTCCCGACTTGA SEQ ID NO: 1628 RPr TGAACTGTGAGGCCAGAGAC SEQ ID NO: 1629 PKD1 NM_000296.2 FPr CAGCACCAGCGATTACGAC SEQ ID NO: 1630 Probe AGCCATTGTGAGGACTCTCCCAGC SEQ ID NO: 1631 RPr CTGAATAGGCCCACGTCC SEQ ID NO: 1632 PKR2 NM_002654.3 FPr CCGCCTGGACATTGATTCAC SEQ ID NO: 1633 Probe ACCCATCACAGCCCGGAACACTG SEQ ID NO: 1634 RPr CTGGGCCAATGGTACAGATGA SEQ ID NO: 1635 PLA2G2A NM_000300.2 FPr GCATCCCTCACCCATCCTA SEQ ID NO: 1636 Probe AGGCCAGGCAGGAGCCCTTCTATA SEQ ID NO: 1637 RPr GCTGGAAATCTGCTGGATGT SEQ ID NO: 1638 PLAUR NM_002659.1 FPr CCCATGGATGCTCCTCTGAA SEQ ID NO: 1639 Probe CATTGACTGCCGAGGCCCCATG SEQ ID NO: 1640 RPr CCGGTGGCTACCAGACATTG SEQ ID NO: 1641 PLK NM_005030.2 FPr AATGAATACAGTATTCCCAAGCACAT SEQ ID NO: 1642 Probe AACCCCGTGGCCGCCTCC SEQ ID NO: 1643 RPr TGTCTGAAGCATCTTCTGGATGA SEQ ID NO: 1644 PLK3 NM_004073.2 FPr TGAAGGAGACGTACCGCTG SEQ ID NO: 1645 Probe CAAGCAGGTTCACTACACGCTGCC SEQ ID NO: 1646 RPr CAGGCAGTGAGAGGCTGG SEQ ID NO: 1647 PLOD2 NM_000935.2 FPr CAGGGAGGTGGTTGCAAAT SEQ ID NO: 1648 Probe TCCAGCCTTTTCGTGGTGACTCAA SEQ ID NO: 1649 RPr TCTCCCAGGATGCATGAAG SEQ ID NO: 1650 PMS1 NM_000534.2 FPr CTTACGGTTTTCGTGGAGAAG SEQ ID NO: 1651 Probe CCTCAGCTATACAACAAATTGACCCCAAG SEQ ID NO: 1652 RPr AGCAGCCGTTCTTGTTGTAA SEQ ID NO: 1653 PMS2 NM_000535.2 FPr GATGTGGACTGCCATTCAAA SEQ ID NO: 1654 Probe TCGAAATTTACATCCGGTATCTTCCTGG SEQ ID NO: 1655 RPr TGCGAGATTAGTTGGCTGAG SEQ ID NO: 1656 PPARG NM_005037.3 FPr TGACTTTATGGAGCCCAAGTT SEQ ID NO: 1657 Probe TTCCAGTGCATTGAACTTCACAGCA SEQ ID NO: 1658 RPr GCCAAGTCGCTGTCATCTAA SEQ ID NO: 1659 PPID NM_005038.1 FPr TCCTCATTTGGATGGGAAAC SEQ ID NO: 1660 Probe TTCCTTTAATTACTTGGCCAAACACCACA SEQ ID NO: 1661 RPr CCAATATCCTTGCCACTCCTA SEQ ID NO: 1662 PPM1D NM_003620.1 FPr GCCATCCGCAAAGGCTTT SEQ ID NO: 1663 Probe TCGCTTGTCACCTTGCCATGTGG SEQ ID NO: 1664 RPr GGCCATTCCGCCAGTTTC SEQ ID NO: 1665 PPP2R4 NM_178001.1 FPr GGCTCAGAGCATAAGGCTTC SEQ ID NO: 1666 Probe TTGGTCACTTCTCCCAACTTGGGC SEQ ID NO: 1667 RPr ACGGGAACTCAGAAAACTGG SEQ ID NO: 1668 PR NM_000926.2 FPr GCATCAGGCTGTCATTATGG SEQ ID NO: 1669 Probe TGTCCTTACCTGTGGGAGCTGTAAGGTC SEQ ID NO: 1670 RPr AGTAGTTGTGCTGCCCTTCC SEQ ID NO: 1671 PRDX2 NM_005809.4 FPr GGTGTCCTTCGCCAGATCAC SEQ ID NO: 1672 Probe TTAATGATTTGCCTGTGGGACGCTCC SEQ ID NO: 1673 RPr CAGCCGCAGAGCCTCATC SEQ ID NO: 1674 PRDX3 NM_006793.2 FPr TGACCCCAATGGAGTCATCA SEQ ID NO: 1675 Probe CATTTGAGCGTCAACGATCTCCCAGTG SEQ ID NO: 1676 RPr CCAAGCGGAGGGTTTCTTC SEQ ID NO: 1677 PRDX4 NM_006406.1 FPr TTACCCATTTGGCCTGGATTAA SEQ ID NO: 1678 Probe CCAAGTCCTCCTTGTCTTCGAGGGGT SEQ ID NO: 1679 RPr CTGAAAGAAGTGGAATCCTTATTGG SEQ ID NO: 1680 PRDX6 NM_004905.2 FPr CTGTGAGCCAGAGGATGTCA SEQ ID NO: 1681 Probe CTGCCAATTGTGTTTTCCTGCAGC SEQ ID NO: 1682 RPr TGTGATGACACCAGGATGTG SEQ ID NO: 1683 PRKCA NM_002737.1 FPr CAAGCAATGCGTCATCAATGT SEQ ID NO: 1684 Probe CAGCCTCTGCGGAATGGATCACACT SEQ ID NO: 1685 RPr GTAAATCCGCCCCCTCTTCT SEQ ID NO: 1686 PRKCB1 NM_002738.5 FPr GACCCAGCTCCACTCCTG SEQ ID NO: 1687 Probe CCAGACCATGGACCGCCTGTACTT SEQ ID NO: 1688 RPr CCCATTCACGTACTCCATCA SEQ ID NO: 1689 PRKCD NM_006254.1 FPr CTGACACTTGCCGCAGAGAA SEQ ID NO: 1690 Probe CCCTTTCTCACCCACCTCATCTGCAC SEQ ID NO: 1691 RPr AGGTGGTCCTTGGTCTGGAA SEQ ID NO: 1692 PRKR NM_002759.1 FPr GCGATACATGAGCCCAGAACA SEQ ID NO: 1693 Probe AGGTCCACTTCCTTTCCATAGTCTTGCGA SEQ ID NO: 1694 RPr TCAGCAAGAATTAGCCCCAAAG SEQ ID NO: 1695 pS2 NM_003225.1 FPr GCCCTCCCAGTGTGCAAAT SEQ ID NO: 1696 Probe TGCTGTTTCGACGACACCGTTCG SEQ ID NO: 1697 RPr CGTCGATGGTATTAGGATAGAAGCA SEQ ID NO: 1698 PTCH NM_000264.2 FPr CCACGACAAAGCCGACTAC SEQ ID NO: 1699 Probe CCTGAAACAAGGCTGAGAATCCCG SEQ ID NO: 1700 RPr TACTCGATGGGCTCTGCTG SEQ ID NO: 1701 PTEN NM_000314.1 FPr TGGCTAAGTGAAGATGACAATCATG SEQ ID NO: 1702 Probe CCTTTCCAGCTTTACAGTGAATTGCTGCA SEQ ID NO: 1703 RPr TGCACATATCATTACACCAGTTCGT SEQ ID NO: 1704 PTGER3 NM_000957.2 FPr TAACTGGGGCAACCTTTTCT SEQ ID NO: 1705 Probe CCTTTGCCTTCCTGGGGCTCTT SEQ ID NO: 1706 RPr TTGCAGGAAAAGGTGACTGT SEQ ID NO: 1707 PTHLH NM_002820.1 FPr AGTGACTGGGAGTGGGCTAGAA SEQ ID NO: 1708 Probe TGACACCTCCACAACGTCGCTGGA SEQ ID NO: 1709 RPr AAGCCTGTTACCGTGAATCGA SEQ ID NO: 1710 PTHR1 NM_000316.1 FPr CGAGGTACAAGCTGAGATCAAGAA SEQ ID NO: 1711 Probe CCAGTGCCAGTGTCCAGCGGCT SEQ ID NO: 1712 RPr GCGTGCCTTTCGCTTGAA SEQ ID NO: 1713 PTK2 NM_005607.3 FPr GACCGGTCGAATGATAAGGT SEQ ID NO: 1714 Probe ACCAGGCCCGTCACATTCTCGTAC SEQ ID NO: 1715 RPr CTGGACATCTCGATGACAGC SEQ ID NO: 1716 PTK2B NM_004103.3 FPr CAAGCCCAGCCGACCTAAG SEQ ID NO: 1717 Probe CTCCGCAAACCAACCTCCTGGCT SEQ ID NO: 1718 RPr GAACCTGGAACTGCAGCTTTG SEQ ID NO: 1719 PTP4A3 NM_007079.2 FPr CCTGTTCTCGGCACCTTAAA SEQ ID NO: 1720 Probe ACCTGACTGCCCCGGGGTCTAATA SEQ ID NO: 1721 RPr TATTGCCTTCGGGTGTCC SEQ ID NO: 1722 PTP4A3 v2 NM_032611.1 FPr AATATTTGTGCGGGGTATGG SEQ ID NO: 1723 Probe CCAAGAGAAACGAGATTTAAAAACCCA SEQ ID NO: 1724 CC RPr AACGAGATCCCTGTGCTTGT SEQ ID NO: 1725 PTPD1 NM_007039.2 FPr CGCTTGCCTAACTCATACTTTCC SEQ ID NO: 1726 Probe TCCACGCAGCGTGGCACTG SEQ ID NO: 1727 RPr CCATTCAGACTGCGCCACTT SEQ ID NO: 1728 PTPN1 NM_002827.2 FPr AATGAGGAAGTTTCGGATGG SEQ ID NO: 1729 Probe CTGATCCAGACAGCCGACCAGCT SEQ ID NO: 1730 RPr CTTCGATCACAGCCAGGTAG SEQ ID NO: 1731 PTPRF NM_002840.2 FPr TGTTTTAGCTGAGGGACGTG SEQ ID NO: 1732 Probe CCGACGTCCCCAAACCTAGCTAGG SEQ ID NO: 1733 RPr TACCAACCCTGGAATGTTGA SEQ ID NO: 1734 PTPRJ NM_002843.2 FPr AACTTCCGGTACCTCGTTCGT SEQ ID NO: 1735 Probe ACTACATGAAGCAGAGTCCTCCCGAATCG SEQ ID NO: 1736 RPr AGCACTGCAATGCACCAGAA SEQ ID NO: 1737 PTPRO NM_030667.1 FPr CATGGCCTGATCATGGTGT SEQ ID NO: 1738 Probe CCCACAGCAAATGCTGCAGAAAGT SEQ ID NO: 1739 RPr CCATGTGTACAAACTGCAGGA SEQ ID NO: 1740 PTTG1 NM_004219.2 FPr GGCTACTCTGATCTATGTTGATAAGGAA SEQ ID NO: 1741 Probe CACACGGGTGCCTGGTTCTCCA SEQ ID NO: 1742 RPr GCTTCAGCCCATCCTTAGCA SEQ ID NO: 1743 RAB32 NM_006834.2 FPr CCTGCAGCTGTGGGACAT SEQ ID NO: 1744 Probe CGATTTGGCAACATGACCCGAGTA SEQ ID NO: 1745 RPr AGCACCAACAGCTTCCTTG SEQ ID NO: 1746 RAB6C NM_032144.1 FPr GCGACAGCTCCTCTAGTTCCA SEQ ID NO: 1747 Probe TTCCCGAAGTCTCCGCCCG SEQ ID NO: 1748 RPr GGAACACCAGCTTGAATTTCCT SEQ ID NO: 1749 RAC1 NM_006908.3 FPr TGTTGTAAATGTCTCAGCCCC SEQ ID NO: 1750 Probe CGTTCTTGGTCCTGTCCCTTGGA SEQ ID NO: 1751 RPr TTGAGCAAAGCGTACAAAGG SEQ ID NO: 1752 RAD51C NM_058216.1 FPr GAACTTCTTGAGCAGGAGCATACC SEQ ID NO: 1753 Probe AGGGCTTCATAATCACCTTCTGTTC SEQ ID NO: 1754 RPr TCCACCCCCAAGAATATCATCTAGT SEQ ID NO: 1755 RAD54L NM_003579.2 FPr AGCTAGCCTCAGTGACACACATG SEQ ID NO: 1756 Probe ACACAACGTCGGCAGTGCAACCTG SEQ ID NO: 1757 RPr CCGGATCTGACGGCTGTT SEQ ID NO: 1758 RAF1 NM_002880.1 FPr CGTCGTATGCGAGAGTCTGT SEQ ID NO: 1759 Probe TCCAGGATGCCTGTTAGTTCTCAGCA SEQ ID NO: 1760 RPr TGAAGGCGTGAGGTGTAGAA SEQ ID NO: 1761 RALBP1 NM_006788.2 FPr GGTGTCAGATATAAATGTGCAAATGC SEQ ID NO: 1762 Probe TGCTGTCCTGTCGGTCTCAGTACGTTCA SEQ ID NO: 1763 RPr TTCGATATTGCCAGCAGCTATAAA SEQ ID NO: 1764 RANBP2 NM_006267.3 FPr TCCTTCAGCTTTCACACTGG SEQ ID NO: 1765 Probe TCCAGAAGAGTCATGCAACTTCATTTCTG SEQ ID NO: 1766 RPr AAATCCTGTTCCCACCTGAC SEQ ID NO: 1767 ranBP7 NM_006391.1 FPr AACATGATTATCCAAGCCGC SEQ ID NO: 1768 Probe AAGCCAATTTTGTCCACAATGGCA SEQ ID NO: 1769 RPr GCCAACAAGCACTGTTATCG SEQ ID NO: 1770 RANBP9 NM_005493.2 FPr CAAGTCAGTTGAGACGCCAGTT SEQ ID NO: 1771 Probe TTCTATGGCGGCCTGACTTCCTCCA SEQ ID NO: 1772 RPr TGCAGCTCTCGTCCAAAGTG SEQ ID NO: 1773 RAP1GDS1 NM_021159.3 FPr TGTGGATGCTGGATTGATTT SEQ ID NO: 1774 Probe CCACTGGTGCAGCTGCTAAATAGCA SEQ ID NO: 1775 RPr AAGCAGCACTTCCTGGTCTT SEQ ID NO: 1776 RARA NM_000964.1 FPr AGTCTGTGAGAAACGACCGAAAC SEQ ID NO: 1777 Probe TCGGGCTTGGGCACCTCCTTCTT SEQ ID NO: 1778 RPr CGGCGTCAGCGTGTAGCT SEQ ID NO: 1779 RARB NM_016152.2 FPr TGCCTGGACATCCTGATTCT SEQ ID NO: 1780 Probe TGCACCAGGTATACCCCAGAACAAGA SEQ ID NO: 1781 RPr AAGGCCGTCTGAGAAAGTCA SEQ ID NO: 1782 RASSF1 NM_007182.3 FPr AGTGGGAGACACCTGACCTT SEQ ID NO: 1783 Probe TTGATCTTCTGCTCAATCTCAGCTTGAGA SEQ ID NO: 1784 RPr TGATCTGGGCATTGTACTCC SEQ ID NO: 1785 RBM5 NM_005778.1 FPr CGAGAGGGAGAGCAAGACCAT SEQ ID NO: 1786 Probe CTGCGCGGCCTTCCCATCA SEQ ID NO: 1787 RPr TCTCGAATATCGCTCTCTGTGATG SEQ ID NO: 1788 RBX1 NM_014248.2 FPr GGAACCACATTATGGATCTTTGC SEQ ID NO: 1789 Probe TAGAATGTCAAGCTAACCAGGCGTCCGC SEQ ID NO: 1790 RPr CATGCGACAGTACACTCTTCTGAA SEQ ID NO: 1791 RCC1 NM_001269.2 FPr GGGCTGGGTGAGAATGTG SEQ ID NO: 1792 Probe ATACCAGGGCCGGCTTCTTCCTCT SEQ ID NO: 1793 RPr CACAACATCCTCCGGAATG SEQ ID NO: 1794 REG4 NM_032044.2 FPr TGCTAACTCCTGCACAGCC SEQ ID NO: 1795 Probe TCCTCTTCCTTTCTGCTAGCCTGGC SEQ ID NO: 1796 RPr TGCTAGGTTTCCCCTCTGAA SEQ ID NO: 1797 RFC NM_003056.1 FPr TCAAGACCATCATCACTTTCATTGT SEQ ID NO: 1798 Probe CCTCCCGGTCCGCAAGCAGTT SEQ ID NO: 1799 RPr GGATCAGGAAGTACACGGAGTATAACT SEQ ID NO: 1800 RhoB NM_004040.2 FPr AAGCATGAACAGGACTTGACC SEQ ID NO: 1801 Probe CTTTCCAACCCCTGGGGAAGACAT SEQ ID NO: 1802 RPr CCTCCCCAAGTCAGTTGC SEQ ID NO: 1803 rhoC NM_175744.1 FPr CCCGTTCGGTCTGAGGAA SEQ ID NO: 1804 Probe TCCGGTTCGCCATGTCCCG SEQ ID NO: 1805 RPr GAGCACTCAAGGTAGCCAAAGG SEQ ID NO: 1806 RIZ1 NM_012231.1 FPr CCAGACGAGCGATTAGAAGC SEQ ID NO: 1807 Probe TGTGAGGTGAATGATTTGGGGGA SEQ ID NO: 1808 RPr TCCTCCTCTTCCTCCTCCTC SEQ ID NO: 1809 RNF11 NM_014372.3 FPr ACCCTGGAAGAGATGGATCA SEQ ID NO: 1810 Probe CCATCATACAGATCACACACTCCCGG SEQ ID NO: 1811 RPr ATTGGGTCCCCATAAACAAA SEQ ID NO: 1812 ROCK1 NM_005406.1 FPr TGTGCACATAGGAATGAGCTTC SEQ ID NO: 1813 Probe TCACTCTCTTTGCTGGCCAACTGC SEQ ID NO: 1814 RPr GTTTAGCACGCAATTGCTCA SEQ ID NO: 1815 ROCK2 NM_004850.3 FPr GATCCGAGACCCTCGCTC SEQ ID NO: 1816 Probe CCCATCAACGTGGAGAGCTTGCT SEQ ID NO: 1817 RPr AGGACCAAGGAATTTAAGCCA SEQ ID NO: 1818 RPLPO NM_001002.2 FPr CCATTCTATCATCAACGGGTACAA SEQ ID NO: 1819 Probe TCTCCACAGACAAGGCCAGGACTCG SEQ ID NO: 1820 RPr TCAGCAAGTGGGAAGGTGTAATC SEQ ID NO: 1821 RPS13 NM_001017.2 FPr CAGTCGGCTTTACCCTATCG SEQ ID NO: 1822 Probe CAACTTCAACCAAGTGGGGACGCT SEQ ID NO: 1823 RPr TCTGCTCCTTCACGTCGTC SEQ ID NO: 1824 RRM1 NM_001033.1 FPr GGGCTACTGGCAGCTACATT SEQ ID NO: 1825 Probe CATTGGAATTGCCATTAGTCCCAGC SEQ ID NO: 1826 RPr CTCTCAGCATCGGTACAAGG SEQ ID NO: 1827 RRM2 NM_001034.1 FPr CAGCGGGATTAAACAGTCCT SEQ ID NO: 1828 Probe CCAGCACAGCCAGTTAAAAGATGCA SEQ ID NO: 1829 RPr ATCTGCGTTGAAGCAGTGAG SEQ ID NO: 1830 RTN4 NM_007008.1 FPr GACTGGAGTGGTGTTTGGTG SEQ ID NO: 1831 Probe CCAGCCTATTCCTGCTGCTTTCATTG SEQ ID NO: 1832 RPr CTGTTACGCTCACAATGCTG SEQ ID NO: 1833 RUNX1 NM_001754.2 FPr AACAGAGACATTGCCAACCA SEQ ID NO: 1834 Probe TTGGATCTGCTTGCTGTCCAAACC SEQ ID NO: 1835 RPr GTGATTTGCCCAGGAAGTTT SEQ ID NO: 1836 RXRA NM_002957.3 FPr GCTCTGTTGTGTCCTGTTGC SEQ ID NO: 1837 Probe TCAGTCACAGGAAGGCCAGAGCC SEQ ID NO: 1838 RPr GTACGGAGAAGCCACTTCACA SEQ ID NO: 1839 S100A1 NM_006271.1 FPr TGGACAAGGTGATGAAGGAG SEQ ID NO: 1840 Probe CCTCCCCGTCTCCATTCTCGTCTA SEQ ID NO: 1841 RPr AGCACCACATACTCCTGGAA SEQ ID NO: 1842 S100A2 NM_005978.2 FPr TGGCTGTGCTGGTCACTACCT SEQ ID NO: 1843 Probe CACAAGTACTCCTGCCAAGAGGGCGAC SEQ ID NO: 1844 RPr TCCCCCTTACTCAGCTTGAACT SEQ ID NO: 1845 S100A4 NM_002961.2 FPr GACTGCTGTCATGGCGTG SEQ ID NO: 1846 Probe ATCACATCCAGGGCCTTCTCCAGA SEQ ID NO: 1847 RPr CGAGTACTTGTGGAAGGTGGAC SEQ ID NO: 1848 S100A8 NM_002964.3 FPr ACTCCCTGATAAAGGGGAATTT SEQ ID NO: 1849 Probe CATGCCGTCTACAGGGATGACCTG SEQ ID NO: 1850 RPr TGAGGACACTCGGTCTCTAGC SEQ ID NO: 1851 S100A9 NM_002965.2 FPr CTTTGGGACAGAGTGCAAGA SEQ ID NO: 1852 Probe CGATGACTTGCAAAATGTCGCAGC SEQ ID NO: 1853 RPr TGGTCTCTATGTTGCGTTCC SEQ ID NO: 1854 S100P NM_005980.2 FPr AGACAAGGATGCCGTGGATAA SEQ ID NO: 1855 Probe TTGCTCAAGGACCTGGACGCCAA SEQ ID NO: 1856 RPr GAAGTCCACCTGGGCATCTC SEQ ID NO: 1857 SAT NM_002970.1 FPr CCTTTTACCACTGCCTGGTT SEQ ID NO: 1858 Probe TCCAGTGCTCTTTCGGCACTTCTG SEQ ID NO: 1859 RPr ACAATGCTGTGTCCTTCCG SEQ ID NO: 1860 SBA2 NM_018639.3 FPr GGACTCAACGATGGGCAG SEQ ID NO: 1861 Probe CCCTGTCTGCACCTCCCAGATCTT SEQ ID NO: 1862 RPr CGGAAAGATTCAAAAGCAGG SEQ ID NO: 1863 SDC1 NM_002997.1 FPr GAAATTGACGAGGGGTGTCT SEQ ID NO: 1864 Probe CTCTGAGCGCCTCCATCCAAGG SEQ ID NO: 1865 RPr AGGAGCTAACGGAGAACCTG SEQ ID NO: 1866 SEMA3B NM_004636.1 FPr GCTCCAGGATGTGTTTCTGTTG SEQ ID NO: 1867 Probe TCGCGGGACCACCGGACC SEQ ID NO: 1868 RPr ACGTGGAGAAGACGGCATAGA SEQ ID NO: 1869 SEMA3F NM_004186.1 FPr CGCGAGCCCCTCATTATACA SEQ ID NO: 1870 Probe CTCCCCACAGCGCATCGAGGAA SEQ ID NO: 1871 RPr CACTCGCCGTTGACATCCT SEQ ID NO: 1872 SEMA4B NM_020210.1 FPr TTCCAGCCCAACACAGTGAA SEQ ID NO: 1873 Probe ACTTTGGCCTGCCCGCTCCTCT SEQ ID NO: 1874 RPr GAGTCGGGTCGCCAGGTT SEQ ID NO: 1875 SFRP2 NM_003013.2 FPr CAAGCTGAACGGTGTGTCC SEQ ID NO: 1876 Probe CAGCACCGATTTCTTCAGGTCCCT SEQ ID NO: 1877 RPr TGCAAGCTGTCTTTGAGCC SEQ ID NO: 1878 SFRP4 NM_003014.2 FPr TACAGGATGAGGCTGGGC SEQ ID NO: 1879 Probe CCTGGGACAGCCTATGTAAGGCCA SEQ ID NO: 1880 RPr GTTGTTAGGGCAAGGGGC SEQ ID NO: 1881 SGCB NM_000232.1 FPr CAGTGGAGACCAGTTGGGTAGTG SEQ ID NO: 1882 Probe CACACATGCAGAGCTTGTAGCGTACCCA SEQ ID NO: 1883 RPr CCTTGAAGAGCGTCCCATCA SEQ ID NO: 1884 SHC1 NM_003029.3 FPr CCAACACCTTCTTGGCTTCT SEQ ID NO: 1885 Probe CCTGTGTTCTTGCTGAGCACCCTC SEQ ID NO: 1886 RPr CTGTTATCCCAACCCAAACC SEQ ID NO: 1887 SHH NM_000193.2 FPr GTCCAAGGCACATATCCACTG SEQ ID NO: 1888 Probe CACCGAGTTCTCTGCTTTCACCGA SEQ ID NO: 1889 RPr GAAGCAGCCTCCCGATTT SEQ ID NO: 1890 SI NM_001041.1 FPr AACGGACTCCCTCAATTTGT SEQ ID NO: 1891 Probe TGTCCATGGTCATGCAAATCTTGC SEQ ID NO: 1892 RPr GAAATTGCAGGGTCCAAGAT SEQ ID NO: 1893 Siah-1 NM_003031.2 FPr TTGGCATTGGAACTACATTCA SEQ ID NO: 1894 Probe TCCGCGGTATCCTCGGATTAGTTC SEQ ID NO: 1895 RPr GGTATGGAGAAGGGGGTCC SEQ ID NO: 1896 SIAT4A NM_003033.2 FPr AACCACAGTTGGAGGAGGAC SEQ ID NO: 1897 Probe CAGAGACAGTTTCCCTCCCCGCT SEQ ID NO: 1898 RPr CGAAGGAAGGGTGTTGGTAT SEQ ID NO: 1899 SIAT7B NM_006456.1 FPr TCCAGCCCAAATCCTCCT SEQ ID NO: 1900 Probe TGGCACATCCTACCCCAGATGCTA SEQ ID NO: 1901 RPr GGTGTCCTGGAGTCCTTGAA SEQ ID NO: 1902 SIM2 NM_005069.2 FPr GATGGTAGGAAGGGATGTGC SEQ ID NO: 1903 Probe CGCCTCTCCACGCACTCAGCTAT SEQ ID NO: 1904 RPr CACAAGGAGCTGTGAATGAGG SEQ ID NO: 1905 SIN3A NM_015477.1 FPr CCAGAGTCATGCTCATCCAG SEQ ID NO: 1906 Probe CTGTCCCTGCACTGGTGCAACTG SEQ ID NO: 1907 RPr CCACCTTCAGCCTCTGAAAT SEQ ID NO: 1908 SIR2 NM_012238.3 FPr AGCTGGGGTGTCTGTTTCAT SEQ ID NO: 1909 Probe CCTGACTTCAGGTCAAGGGATGG SEQ ID NO: 1910 RPr ACAGCAAGGCGAGCATAAAT SEQ ID NO: 1911 SKP1A NM_006930.2 FPr CCATTGCCTTTGCTTTGTTCAT SEQ ID NO: 1912 Probe TCCCATGGTTTTTATTCTGCCCTGCTG SEQ ID NO: 1913 RPr TTCCGGATTTCCTTTCTTTGC SEQ ID NO: 1914 SKP2 NM_005983.2 FPr AGTTGCAGAATCTAAGCCTGGAA SEQ ID NO: 1915 Probe CCTGCGGCTTTCGGATCCCA SEQ ID NO: 1916 RPr TGAGTTTTTTGCGAGAGTATTGACA SEQ ID NO: 1917 SLC25A3 NM_213611.1 FPr TCTGCCAGTGCTGAATTCTT SEQ ID NO: 1918 Probe TGCTGACATTGCCCTGGCTCCTAT SEQ ID NO: 1919 RPr TTCGAACCTTAGCAGCTTCC SEQ ID NO: 1920 SLC2A1 NM_006516.1 FPr GCCTGAGTCTCCTGTGCC SEQ ID NO: 1921 Probe ACATCCCAGGCTTCACCCTGAATG SEQ ID NO: 1922 RPr AGTCTCCACCCTCAGGCAT SEQ ID NO: 1923 SLC31A1 NM_001859.2 FPr CCGTTCGAAGAGTCGTGAG SEQ ID NO: 1924 Probe TCTCCGAATCTTAACCCGTCACCC SEQ ID NO: 1925 RPr AGTCCAGCCACTAGCACCTC SEQ ID NO: 1926 SLC5A8 NM_145913.2 FPr CCTGCTTTCAACCACATTGA SEQ ID NO: 1927 Probe TCCCATTGCTCTTGCCACTCTGAT SEQ ID NO: 1928 RPr AGAGCAGCTTCACAAACGAG SEQ ID NO: 1929 SLC7A5 NM_003486.4 FPr GCGCAGAGGCCAGTTAAA SEQ ID NO: 1930 Probe AGATCACCTCCTCGAACCCACTCC SEQ ID NO: 1931 RPr AGCTGAGCTGTGGGTTGC SEQ ID NO: 1932 SLPI NM_003064.2 FPr ATGGCCAATGTTTGATGCT SEQ ID NO: 1933 Probe TGGCCATCCATCTCACAGAAATTGG SEQ ID NO: 1934 RPr ACACTTCAAGTCACGCTTGC SEQ ID NO: 1935 SMARCA3 NM_003071.2 FPr AGGGACTGTCCTGGCACAT SEQ ID NO: 1936 Probe AGCAAAAGACCCAGGACATCTGCA SEQ ID NO: 1937 RPr CAACAAATTTGCCGCAGTC SEQ ID NO: 1938 SNAI1 NM_005985.2 FPr CCCAATCGGAAGCCTAACTA SEQ ID NO: 1939 Probe TCTGGATTAGAGTCCTGCAGCTCGC SEQ ID NO: 1940 RPr GTAGGGCTGCTGGAAGGTAA SEQ ID NO: 1941 SNAI2 NM_003068.3 FPr GGCTGGCCAAACATAAGCA SEQ ID NO: 1942 Probe CTGCACTGCGATGCCCAGTCTAGAAAATC SEQ ID NO: 1943 RPr TCCTTGTCACAGTATTTACAGCTGAA SEQ ID NO: 1944 SNRPF NM_003095.1 FPr GGCTGGTCGGCAGAGAGTAG SEQ ID NO: 1945 Probe AAACTCATGTAAACCACGGCCGAATGTTG SEQ ID NO: 1946 RPr TGAGGAAAGGTTTGGGATTGA SEQ ID NO: 1947 SOD1 NM_000454.3 FPr TGAAGAGAGGCATGTTGGAG SEQ ID NO: 1948 Probe TTTGTCAGCAGTCACATTGCCCAA SEQ ID NO: 1949 RPr AATAGACACATCGGCCACAC SEQ ID NO: 1950 SOD2 NM_000636.1 FPr GCTTGTCCAAATCAGGATCCA SEQ ID NO: 1951 Probe AACAACAGGCCTTATTCCACTGCTGGG SEQ ID NO: 1952 RPr AGCGTGCTCCCACACATCA SEQ ID NO: 1953 SOS1 NM_005633.2 FPr TCTGCACCAAATTCTCCAAG SEQ ID NO: 1954 Probe AACACCGTTAACACCTCCGCCTG SEQ ID NO: 1955 RPr GTGGTACTGGAAGCACCAGA SEQ ID NO: 1956 SOX17 NM_022454.2 FPr TCGTGTGCAAGCCTGAGA SEQ ID NO: 1957 Probe CTCCCCTACCAGGGGCATGACTC SEQ ID NO: 1958 RPr CTGTCGGGGAGATTCACAC SEQ ID NO: 1959 SPARC NM_003118.1 FPr TCTTCCCTGTACACTGGCAGTTC SEQ ID NO: 1960 Probe TGGACCAGCACCCCATTGACGG SEQ ID NO: 1961 RPr AGCTCGGTGTGGGAGAGGTA SEQ ID NO: 1962 SPINT2 NM_021102.1 FPr AGGAATGCAGCGGATTCCT SEQ ID NO: 1963 Probe CCCAAGTGCTCCCAGAAGGCAGG SEQ ID NO: 1964 RPr TCGCTGGAGTGGTCTTCAGA SEQ ID NO: 1965 SPRY1 AK026960.1 FPr CAGACCAGTCCCTGGTCATAGG SEQ ID NO: 1966 Probe CTGGGTCCGGATTGCCCTTTCAG SEQ ID NO: 1967 RPr CCTTCAAGTCATCCACAATCAGTT SEQ ID NO: 1968 SPRY2 NM_005842.1 FPr TGTGGCAAGTGCAAATGTAA SEQ ID NO: 1969 Probe CAGAGGCCTTGGGTAGGTGCACTC SEQ ID NO: 1970 RPr GTCGCAGATCCAGTCTGATG SEQ ID NO: 1971 SR-A1 NM_021228.1 FPr AGATGGAAGAAGCCAACCTG SEQ ID NO: 1972 Probe CTGGATCAGCTCCTGGGCCTTC SEQ ID NO: 1973 RPr CTGTGGCTGAGGATCTGGT SEQ ID NO: 1974 ST14 NM_021978.2 FPr TGACTGCACATGGAACATTG SEQ ID NO: 1975 Probe AGGTGCCCAACAACCAGCATGT SEQ ID NO: 1976 RPr AAGAATTTGAAGCGCACCTT SEQ ID NO: 1977 STAT1 NM_007315.1 FPr GGGCTCAGCTTTCAGAAGTG SEQ ID NO: 1978 Probe TGGCAGTTTTCTTCTGTCACCAAAA SEQ ID NO: 1979 RPr ACATGTTCAGCTGGTCCACA SEQ ID NO: 1980 STAT3 NM_003150.1 FPr TCACATGCCACTTTGGTGTT SEQ ID NO: 1981 Probe TCCTGGGAGAGATTGACCAGCA SEQ ID NO: 1982 RPr CTTGCAGGAAGCGGCTATAC SEQ ID NO: 1983 STAT5A NM_003152.1 FPr GAGGCGCTCAACATGAAATTC SEQ ID NO: 1984 Probe CGGTTGCTCTGCACTTCGGCCT SEQ ID NO: 1985 RPr GCCAGGAACACGAGGTTCTC SEQ ID NO: 1986 STAT5B NM_012448.1 FPr CCAGTGGTGGTGATCGTTCA SEQ ID NO: 1987 Probe CAGCCAGGACAACAATGCGACGG SEQ ID NO: 1988 RPr GCAAAAGCATTGTCCCAGAGA SEQ ID NO: 1989 STC1 NM_003155.1 FPr CTCCGAGGTGAGGAGGACT SEQ ID NO: 1990 Probe CACATCAAACGCACATCCCATGAG SEQ ID NO: 1991 RPr ACCTCTCCCTGGTTATGCAC SEQ ID NO: 1992 STK11 NM_000455.3 FPr GGACTCGGAGACGCTGTG SEQ ID NO: 1993 Probe TTCTTGAGGATCTTGACGGCCCTC SEQ ID NO: 1994 RPr GGGATCCTTCGCAACTTCTT SEQ ID NO: 1995 STK15 NM_003600.1 FPr CATCTTCCAGGAGGACCACT SEQ ID NO: 1996 Probe CTCTGTGGCACCCTGGACTACCTG SEQ ID NO: 1997 RPr TCCGACCTTCAATCATTTCA SEQ ID NO: 1998 STMN1 NM_005563.2 FPr AATACCCAACGCACAAATGA SEQ ID NO: 1999 Probe CACGTTCTCTGCCCCGTTTCTTG SEQ ID NO: 2000 RPr GGAGACAATGCAAACCACAC SEQ ID NO: 2001 STMY3 NM_005940.2 FPr CCTGGAGGCTGCAACATACC SEQ ID NO: 2002 Probe ATCCTCCTGAAGCCCTTTTCGCAGC SEQ ID NO: 2003 RPr TACAATGGCTTTGGAGGATAGCA SEQ ID NO: 2004 STS NM_000351.2 FPr GAAGATCCCTTTCCTCCTACTGTTC SEQ ID NO: 2005 Probe CTTCGTGGCTCTCGGCTTCCCA SEQ ID NO: 2006 RPr GGATGATGTTCGGCCTTGAT SEQ ID NO: 2007 SURV NM_001168.1 FPr TGTTTTGATTCCCGGGCTTA SEQ ID NO: 2008 Probe TGCCTTCTTCCTCCCTCACTTCTCACCT SEQ ID NO: 2009 RPr CAAAGCTGTCAGCTCTAGCAAAAG SEQ ID NO: 2010 TAGLN NM_003186.2 FPr GATGGAGCAGGTGGCTCAGT SEQ ID NO: 2011 Probe CCCAGAGTCCTCAGCCGCCTTCAG SEQ ID NO: 2012 RPr AGTCTGGAACATGTCAGTCTTGATG SEQ ID NO: 2013 TBP NM_003194.1 FPr GCCCGAAACGCCGAATATA SEQ ID NO: 2014 Probe TACCGCAGCAAACCGCTTGGG SEQ ID NO: 2015 RPr CGTGGCTCTCTTATCCTCATGAT SEQ ID NO: 2016 TCF-1 NM_000545.3 FPr GAGGTCCTGAGCACTGCC SEQ ID NO: 2017 Probe CTGGGTTCACAGGCTCCTTTGTCC SEQ ID NO: 2018 RPr GATGTGGGACCATGCTTGT SEQ ID NO: 2019 TCF-7 NM_003202.2 FPr GCAGCTGCAGTCAACAGTTC SEQ ID NO: 2020 Probe AAGTCATGGCCCAAATCCAGTGTG SEQ ID NO: 2021 RPr CTGTGAATGGGGAGGGGT SEQ ID NO: 2022 TCF7L1 NM_031283.1 FPr CCGGGACACTTTCCAGAAG SEQ ID NO: 2023 Probe TCTCACTTCGGCGAAATAGTCCCG SEQ ID NO: 2024 RPr AGAACGCGCTGTCCTGAG SEQ ID NO: 2025 TCF7L2 NM_030756.1 FPr CCAATCACGACAGGAGGATT SEQ ID NO: 2026 Probe AGACACCCCTACCCCACAGCTCTG SEQ ID NO: 2027 RPr TGGACACGGAAGCATTGAC SEQ ID NO: 2028 TCFL4 NM_170607.2 FPr CTGACTGCTCTGCTTAAAGGTGAA SEQ ID NO: 2029 Probe TAGCAGGAACAACAACAAAAGCCAACC SEQ ID NO: 2030 AA RPr ATGTCTTGCACTGGCTACCTTGT SEQ ID NO: 2031 TEK NM_000459.1 FPr ACTTCGGTGCTACTTAACAACTTACATC SEQ ID NO: 2032 Probe AGCTCGGACCACGTACTGCTCCCTG SEQ ID NO: 2033 RPr CCTGGGCCTTGGTGTTGAC SEQ ID NO: 2034 TERC U86046.1 FPr AAGAGGAACGGAGCGAGTC SEQ ID NO: 2035 Probe CACGTCCCACAGCTCAGGGAATC SEQ ID NO: 2036 RPr ATGTGTGAGCCGAGTCCTG SEQ ID NO: 2037 TERT NM_003219.1 FPr GACATGGAGAACAAGCTGTTTGC SEQ ID NO: 2038 Probe ACCAAACGCAGGAGCAGCCCG SEQ ID NO: 2039 RPr GAGGTGTCACCAACAAGAAATCAT SEQ ID NO: 2040 TFF3 NM_003226.1 FPr AGGCACTGTTCATCTCAGTTTTTCT SEQ ID NO: 2041 Probe CAGAAAGCTTGCCGGGAGCAAAGG SEQ ID NO: 2042 RPr CATCAGGCTCCAGATATGAACTTTC SEQ ID NO: 2043 TGFA NM_003236.1 FPr GGTGTGCCACAGACCTTCCT SEQ ID NO: 2044 Probe TTGGCCTGTAATCACCTGTGCAGCCTT SEQ ID NO: 2045 RPr ACGGAGTTCTTGACAGAGTTTTGA SEQ ID NO: 2046 TGFB2 NM_003238.1 FPr ACCAGTCCCCCAGAAGACTA SEQ ID NO: 2047 Probe TCCTGAGCCCGAGGAAGTCCC SEQ ID NO: 2048 RPr CCTGGTGCTGTTGTAGATGG SEQ ID NO: 2049 TGFB3 NM_003239.1 FPr GGATCGAGCTCTTCCAGATCCT SEQ ID NO: 2050 Probe CGGCCAGATGAGCACATTGCC SEQ ID NO: 2051 RPr GCCACCGATATAGCGCTGTT SEQ ID NO: 2052 TGFBI NM_000358.1 FPr GCTACGAGTGCTGTCCTGG SEQ ID NO: 2053 Probe CCTTCTCCCCAGGGACCTTTTCAT SEQ ID NO: 2054 RPr AGTGGTAGGGCTGCTGGAC SEQ ID NO: 2055 TGFBR1 NM_004612.1 FPr GTCATCACCTGGCCTTGG SEQ ID NO: 2056 Probe AGCAATGACAGCTGCCAGTTCCAC SEQ ID NO: 2057 RPr GCAGACGAAGCACACTGGT SEQ ID NO: 2058 TGFBR2 NM_003242.2 FPr AACACCAATGGGTTCCATCT SEQ ID NO: 2059 Probe TTCTGGGCTCCTGATTGCTCAAGC SEQ ID NO: 2060 RPr CCTCTTCATCAGGCCAAACT SEQ ID NO: 2061 THBS1 NM_003246.1 FPr CATCCGCAAAGTGACTGAAGAG SEQ ID NO: 2062 Probe CCAATGAGCTGAGGCGGCCTCC SEQ ID NO: 2063 RPr GTACTGAACTCCGTTGTGATAGCATAG SEQ ID NO: 2064 THY1 NM_006288.2 FPr GGACAAGACCCTCTCAGGCT SEQ ID NO: 2065 Probe CAAGCTCCCAAGAGCTTCCAGAGC SEQ ID NO: 2066 RPr TTGGAGGCTGTGGGTCAG SEQ ID NO: 2067 TIMP1 NM_003254.1 FPr TCCCTGCGGTCCCAGATAG SEQ ID NO: 2068 Probe ATCCTGCCCGGAGTGGAACTGAAGC SEQ ID NO: 2069 RPr GTGGGAACAGGGTGGACACT SEQ ID NO: 2070 TIMP2 NM_003255.2 FPr TCACCCTCTGTGACTTCATCGT SEQ ID NO: 2071 Probe CCCTGGGACACCCTGAGCACCA SEQ ID NO: 2072 RPr TGTGGTTCAGGCTCTTCTTCTG SEQ ID NO: 2073 TIMP3 NM_000362.2 FPr CTACCTGCCTTGCTTTGTGA SEQ ID NO: 2074 Probe CCAAGAACGAGTGTCTCTGGACCG SEQ ID NO: 2075 RPr ACCGAAATTGGAGAGCATGT SEQ ID NO: 2076 TJP1 NM_003257.1 FPr ACTTTGCTGGGACAAAGGTC SEQ ID NO: 2077 Probe CTCGGGCCTGCCCACTTCTTC SEQ ID NO: 2078 RPr CACATGGACTCCTCAGCATC SEQ ID NO: 2079 TK1 NM_003258.1 FPr GCCGGGAAGACCGTAATTGT SEQ ID NO: 2080 Probe CAAATGGCTTCCTCTGGAAGGTCCCA SEQ ID NO: 2081 RPr CAGCGGCACCAGGTTCAG SEQ ID NO: 2082 TLN1 NM_006289.2 FPr AAGCAGAAGGGAGAGCGTAAGA SEQ ID NO: 2083 Probe CTTCCAGGCACACAAGAATTGTGGGC SEQ ID NO: 2084 RPr CCTTGGCCTCAATCTCACTCA SEQ ID NO: 2085 TMEPAI NM_020182.3 FPr CAGAAGGATGCCTGTGGC SEQ ID NO: 2086 Probe ATTCCGTTGCCTGACACTGTGCTC SEQ ID NO: 2087 RPr GTAGACCTGCGGCTCTGG SEQ ID NO: 2088 TMSB10 NM_021103.2 FPr GAAATCGCCAGCTTCGATAA SEQ ID NO: 2089 Probe CGTCTCCGTTTTCTTCAGCTTGGC SEQ ID NO: 2090 RPr GTCGGCAGGGTGTTCTTTT SEQ ID NO: 2091 TMSB4X NM_021109.2 FPr CACATCAAAGAACTACTGACAACGAA SEQ ID NO: 2092 Probe CCGCGCCTGCCTTTCCCA SEQ ID NO: 2093 RPr CCTGCCAGCCAGATAGATAGACA SEQ ID NO: 2094 TNC NM_002160.1 FPr AGCTCGGAACCTCACCGT SEQ ID NO: 2095 Probe CAGCCTTCGGGCTGTGGACATAC SEQ ID NO: 2096 RPr GTAGCAGCCTTGAGGCCC SEQ ID NO: 2097 TNF NM_000594.1 FPr GGAGAAGGGTGACCGACTCA SEQ ID NO: 2098 Probe CGCTGAGATCAATCGGCCCGACTA SEQ ID NO: 2099 RPr TGCCCAGACTCGGCAAAG SEQ ID NO: 2100 TNFRSF5 NM_001250.3 FPr TCTCACCTCGCTATGGTTCGT SEQ ID NO: 2101 Probe TGCCTCTGCAGTGCGTCCTCTGG SEQ ID NO: 2102 RPr GATGGACAGCGGTCAGCAA SEQ ID NO: 2103 TNFRSF6B NM_003823.2 FPr CCTCAGCACCAGGGTACCA SEQ ID NO: 2104 Probe TGACGGCACGCTCACACTCCTCAG SEQ ID NO: 2105 RPr TGTCCTGGAAAGCCACAAAGT SEQ ID NO: 2106 TNFSF4 NM_003326.2 FPr CTTCATCTTCCCTCTACCCAGA SEQ ID NO: 2107 Probe CAGGGGTTGGACCCTTTCCATCTT SEQ ID NO: 2108 RPr GCTGCATTTCCCACATTCTC SEQ ID NO: 2109 TOP2A NM_001067.1 FPr AATCCAAGGGGGAGAGTGAT SEQ ID NO: 2110 Probe CATATGGACTTTGACTCAGCTGTGGC SEQ ID NO: 2111 RPr GTACAGATTTTGCCCGAGGA SEQ ID NO: 2112 TOP2B NM_001068.1 FPr TGTGGACATCTTCCCCTCAGA SEQ ID NO: 2113 Probe TTCCCTACTGAGCCACCTTCTCTG SEQ ID NO: 2114 RPr CTAGCCCGACCGGTTCGT SEQ ID NO: 2115 TP NM_001953.2 FPr CTATATGCAGCCAGAGATGTGACA SEQ ID NO: 2116 Probe ACAGCCTGCCACTCATCACAGCC SEQ ID NO: 2117 RPr CCACGAGTTTCTTACTGAGAATGG SEQ ID NO: 2118 TP53BP1 NM_005657.1 FPr TGCTGTTGCTGAGTCTGTTG SEQ ID NO: 2119 Probe CCAGTCCCCAGAAGACCATGTCTG SEQ ID NO: 2120 RPr CTTGCCTGGCTTCACAGATA SEQ ID NO: 2121 TP53BP2 NM_005426.1 FPr GGGCCAAATATTCAGAAGC SEQ ID NO: 2122 Probe CCACCATAGCGGCCATGGAG SEQ ID NO: 2123 RPr GGATGGGTATGATGGGACAG SEQ ID NO: 2124 TP53I3 NM_004881.2 FPr GCGGACTTAATGCAGAGACA SEQ ID NO: 2125 Probe CAGTATGACCCACCTCCAGGAGCC SEQ ID NO: 2126 RPr TCAAGTCCCAAAATGTTGCT SEQ ID NO: 2127 TRAG3 NM_004909.1 FPr GACGCTGGTCTGGTGAAGATG SEQ ID NO: 2128 Probe CCAGGAAACCACGAGCCTCCAGC SEQ ID NO: 2129 RPr TGGGTGGTTGTTGGACAATG SEQ ID NO: 2130 TRAIL NM_003810.1 FPr CTTCACAGTGCTCCTGCAGTCT SEQ ID NO: 2131 Probe AAGTACACGTAAGTTACAGCCACACA SEQ ID NO: 2132 RPr CATCTGCTTCAGCTCGTTGGT SEQ ID NO: 2133 TS NM_001071.1 FPr GCCTCGGTGTGCCTTTCA SEQ ID NO: 2134 Probe CATCGCCAGCTACGCCCTGCTC SEQ ID NO: 2135 RPr CGTGATGTGCGCAATCATG SEQ ID NO: 2136 TST NM_003312.4 FPr GGAGCCGGATGCAGTAGGA SEQ ID NO: 2137 Probe ACCACGGATATGGCCCGAGTCCA SEQ ID NO: 2138 RPr AAGTCCATGAAAGGCATGTTGA SEQ ID NO: 2139 TUBA1 NM_006000.1 FPr TGTCACCCCGACTCAACGT SEQ ID NO: 2140 Probe AGACGCACCGCCCGGACTCAC SEQ ID NO: 2141 RPr ACGTGGACTGAGATGCATTCAC SEQ ID NO: 2142 TUBB NM_001069.1 FPr CGAGGACGAGGCTTAAAAAC SEQ ID NO: 2143 Probe TCTCAGATCAATCGTGCATCCTTAGTGAA SEQ ID NO: 2144 RPr ACCATGCTTGAGGACAACAG SEQ ID NO: 2145 TUFM NM_003321.3 FPr GTATCACCATCAATGCGGC SEQ ID NO: 2146 Probe CATGTGGAGTATAGCACTGCCGCC SEQ ID NO: 2147 RPr CAGTCTGTGTGGGCGTAGTG SEQ ID NO: 2148 TULP3 NM_003324.2 FPr TGTGTATAGTCCTGCCCCTCAA SEQ ID NO: 2149 Probe CCGGATTATCCGACATCTTACTGTGA SEQ ID NO: 2150 RPr CCCGATCCATTCCCCTTTTA SEQ ID NO: 2151 tusc4 NM_006545.4 FPr GGAGGAGCTAAATGCCTCAG SEQ ID NO: 2152 Probe ACTCATCAATGGGCAGAGTGCACC SEQ ID NO: 2153 RPr CCTTCAAGTGGATGGTGTTG SEQ ID NO: 2154 UBB NM_018955.1 FPr GAGTCGACCCTGCACCTG SEQ ID NO: 2155 Probe AATTAACAGCCACCCCTCAGGCG SEQ ID NO: 2156 RPr GCGAATGCCATGACTGAA SEQ ID NO: 2157 UBC NM_021009.2 FPr ACGCACCCTGTCTGACTACA SEQ ID NO: 2158 Probe CATCCAGAAAGAGTCCACCCTGCA SEQ ID NO: 2159 RPr ACCTCTAAGACGGAGCACCA SEQ ID NO: 2160 UBE2C NM_007019.2 FPr TGTCTGGCGATAAAGGGATT SEQ ID NO: 2161 Probe TCTGCCTTCCCTGAATCAGACAACC SEQ ID NO: 2162 RPr ATGGTCCCTACCCATTTGAA SEQ ID NO: 2163 UBE2M NM_003969.1 FPr CTCCATAATTTATGGCCTGCAGTA SEQ ID NO: 2164 Probe TCTTCTTGGAGCCCAACCCCGAG SEQ ID NO: 2165 RPr TGCGGCCTCCTTGTTCAG SEQ ID NO: 2166 UBL1 NM_003352.3 FPr GTGAAGCCACCGTCATCATG SEQ ID NO: 2167 Probe CTGACCAGGAGGCAAAACCTTCAACTGA SEQ ID NO: 2168 RPr CCTTCCTTCTTATCCCCCAAGT SEQ ID NO: 2169 UCP2 NM_003355.2 FPr ACCATGCTCCAGAAGGAGG SEQ ID NO: 2170 Probe CCCCGAGCCTTCTACAAAGGGTTC SEQ ID NO: 2171 RPr AACCCAAGCGGAGAAAGG SEQ ID NO: 2172 UGT1A1 NM_000463.2 FPr CCATGCAGCCTGGAATTTG SEQ ID NO: 2173 Probe CTACCCAGTGCCCCAACCCATTCTC SEQ ID NO: 2174 RPr GAGAGGCCTGGGCACGTA SEQ ID NO: 2175 UMPS NM_000373.1 FPr TGCGGAAATGAGCTCCAC SEQ ID NO: 2176 Probe CCCTGGCCACTGGGGACTACACTA SEQ ID NO: 2177 RPr CCTCAGCCATTCTAACCGC SEQ ID NO: 2178 UNC5A XM_030300.7 FPr GACAGCTGATCCAGGAGCC SEQ ID NO: 2179 Probe CGGGTCCTGCACTTCAAGGACAGT SEQ ID NO: 2180 RPr ATGGATAGGCGCAGGTTG SEQ ID NO: 2181 UNC5B NM_170744.2 FPr AGAACGGAGGCCGTGACT SEQ ID NO: 2182 Probe CGGGACGCTGCTCGACTCTAAGAA SEQ ID NO: 2183 RPr CATGCACAGCCCATCTGT SEQ ID NO: 2184 UNC5C NM_003728.2 FPr CTGAACACAGTGGAGCTGGT SEQ ID NO: 2185 Probe ACCTGCCGCACACAGAGTTTGC SEQ ID NO: 2186 RPr CTGGAAGATCTGCCCTTCTC SEQ ID NO: 2187 upa NM_002658.1 FPr GTGGATGTGCCCTGAAGGA SEQ ID NO: 2188 Probe AAGCCAGGCGTCTACACGAGAGTCTCAC SEQ ID NO: 2189 RPr CTGCGGATCCAGGGTAAGAA SEQ ID NO: 2190 UPP1 NM_003364.2 FPr ACGGGTCCTGCCTCAGTT SEQ ID NO: 2191 Probe TCAGCTTTCTCTGCATTGGCTCCC SEQ ID NO: 2192 RPr CGGGGCAATCATTGTGAC SEQ ID NO: 2193 VCAM1 NM_001078.2 FPr TGGCTTCAGGAGCTGAATACC SEQ ID NO: 2194 Probe CAGGCACACACAGGTGGGACACAAAT SEQ ID NO: 2195 RPr TGCTGTCGTGATGAGAAAATAGTG SEQ ID NO: 2196 VCL NM_003373.2 FPr GATACCACAACTCCCATCAAGCT SEQ ID NO: 2197 Probe AGTGGCAGCCACGGCGCC SEQ ID NO: 2198 RPr TCCCTGTTAGGCGCATCAG SEQ ID NO: 2199 VCP NM_007126.2 FPr GGCTTTGGCAGCTTCAGAT SEQ ID NO: 2200 Probe AGCTCCACCCTGGTTCCCTGAAG SEQ ID NO: 2201 RPr CTCCACTGCCCTGACTGG SEQ ID NO: 2202 VDAC1 NM_003374.1 FPr GCTGCGACATGGATTTCGA SEQ ID NO: 2203 Probe TTGCTGGGCCTTCCATCCGG SEQ ID NO: 2204 RPr CCAGCCCTCGTAACCTAGCA SEQ ID NO: 2205 VDAC2 NM_003375.2 FPr ACCCACGGACAGACTTGC SEQ ID NO: 2206 Probe CGCGTCCAATGTGTATTCCTCCAT SEQ ID NO: 2207 RPr AGCTTTGCCAAGGTCAGC SEQ ID NO: 2208 VDR NM_000376.1 FPr GCCCTGGATTTCAGAAAGAG SEQ ID NO: 2209 Probe CAAGTCTGGATCTGGGACCCTTTCC SEQ ID NO: 2210 RPr AGTTACAAGCCAGGGAAGGA SEQ ID NO: 2211 VEGF NM_003376.3 FPr CTGCTGTCTTGGGTGCATTG SEQ ID NO: 2212 Probe TTGCCTTGCTGCTCTACCTCCACCA SEQ ID NO: 2213 RPr GCAGCCTGGGACCACTTG SEQ ID NO: 2214 VEGF_altsplice1 AF486837.1 FPr TGTGAATGCAGACCAAAGAAAGA SEQ ID NO: 2215 Probe AGAGCAAGACAAGAAAATCCCTGTGGGC SEQ ID NO: 2216 RPr GCTTTCTCCGCTCTGAGCAA SEQ ID NO: 2217 VEGF_altsplice2 AF214570.1 FPr AGCTTCCTACAGCACAACAAAT SEQ ID NO: 2218 Probe TGTCTTGCTCTATCTTTCTTTGGTCTGCA SEQ ID NO: 2219 RPr CTCGGCTTGTCACATTTTTC SEQ ID NO: 2220 VEGFB NM_003377.2 FPr TGACGATGGCCTGGAGTGT SEQ ID NO: 2221 Probe CTGGGCAGCACCAAGTCCGGA SEQ ID NO: 2222 RPr GGTACCGGATCATGAGGATCTG SEQ ID NO: 2223 VEGFC NM_005429.2 FPr CCTCAGCAAGACGTTATTTGAAATT SEQ ID NO: 2224 Probe CCTCTCTCTCAAGGCCCCAAACCAGT SEQ ID NO: 2225 RPr AAGTGTGATTGGCAAAACTGATTG SEQ ID NO: 2226 VIM NM_003380.1 FPr TGCCCTTAAAGGAACCAATGA SEQ ID NO: 2227 Probe ATTTCACGCATCTGGCGTTCCA SEQ ID NO: 2228 RPr GCTTCAACGGCAAAGTTCTCTT SEQ ID NO: 2229 WIF NM_007191.2 FPr TACAAGCTGAGTGCCCAGG SEQ ID NO: 2230 Probe TACAAAAGCCTCCATTTCGGCACC SEQ ID NO: 2231 RPr CACTCGCAGATGCGTCTTT SEQ ID NO: 2232 WISP1 NM_003882.2 FPr AGAGGCATCCATGAACTTCACA SEQ ID NO: 2233 Probe CGGGCTGCATCAGCACACGC SEQ ID NO: 2234 RPr CAAACTCCACAGTACTTGGGTTGA SEQ ID NO: 2235 Wnt-3a NM_033131.2 FPr ACAAAGCTACCAGGGAGTCG SEQ ID NO: 2236 Probe TTTGTCCACGCCATTGCCTCAG SEQ ID NO: 2237 RPr TGAGCGTGTCACTGCAAAG SEQ ID NO: 2238 Wnt-5a NM_003392.2 FPr GTATCAGGACCACATGCAGTACATC SEQ ID NO: 2239 Probe TTGATGCCTGTCTTCGCGCCTTCT SEQ ID NO: 2240 RPr TGTCGGAATTGATACTGGCATT SEQ ID NO: 2241 Wnt-5b NM_032642.2 FPr TGTCTTCAGGGTCTTGTCCA SEQ ID NO: 2242 Probe TTCCGTAAGAGGCCTGGTGCTCTC SEQ ID NO: 2243 RPr GTGCACGTGGATGAAAGAGT SEQ ID NO: 2244 WNT2 NM_003391.1 FPr CGGTGGAATCTGGCTCTG SEQ ID NO: 2245 Probe CTCCCTCTGCTCTTGACCTGGCTC SEQ ID NO: 2246 RPr CCATGAAGAGTTGACCTCGG SEQ ID NO: 2247 WWOX NM_016373.1 FPr ATCGCAGCTGGTGGGTGTA SEQ ID NO: 2248 Probe CTGCTGTTTACCTTGGCGAGGCCTTT SEQ ID NO: 2249 RPr AGCTCCCTGTTGCATGGACTT SEQ ID NO: 2250 XPA NM_000380.2 FPr GGGTAGAGGGAAAAGGGTTC SEQ ID NO: 2251 Probe CAAAGGCTGAACTGGATTCTTAACCAAGA SEQ ID NO: 2252 RPr TGCACCACCATTGCTATTATT SEQ ID NO: 2253 XPC NM_004628.2 FPr GATACATCGTCTGCGAGGAA SEQ ID NO: 2254 Probe TTCAAAGACGTGCTCCTGACTGCC SEQ ID NO: 2255 RPr CTTTCAATGACTGCCTGCTC SEQ ID NO: 2256 XRCC1 NM_006297.1 FPr GGAGATGAAGCCCCCAAG SEQ ID NO: 2257 Probe AGAAGCAACCCCAGACCAAAACCA SEQ ID NO: 2258 RPr GTCCAGCTGCCTGAGTGG SEQ ID NO: 2259 YB-1 NM_004559.1 FPr AGACTGTGGAGTTTGATGTTGTTGA SEQ ID NO: 2260 Probe TTGCTGCCTCCGCACCCTTTTCT SEQ ID NO: 2261 RPr GGAACACCACCAGGACCTGTAA SEQ ID NO: 2262 YWHAH NM_003405.2 FPr CATGGCCTCCGCTATGAA SEQ ID NO: 2263 Probe AGGTTCATTCAGCTCTGTCACCGC SEQ ID NO: 2264 RPr GGAGATTTCGATCTTCATTGGA SEQ ID NO: 2265 zbtb7 NM_015898.2 FPr CTGCGTTCACACCCCAGT SEQ ID NO: 2266 Probe TCTCTCCAGAACAGCTCGCCCTGT SEQ ID NO: 2267 RPr CTCAGCCACGACAGATGGT SEQ ID NO: 2268 ZG16 NM_152338.1 FPr TGCTGAGCCTCCTCTCCTT SEQ ID NO: 2269 Probe TACTCCTCATCACAGTGCCCCTGC SEQ ID NO: 2270 RPr GGATGGGGGTTAGTGATAAGG SEQ ID NO: 2271

TABLE B SEQ ID Gene Locus Link Sequence NO A-Catenin NM_001903.1 CGTTCCGATCCTCTATACTGCATCCCAGGCATGCCTACAGCACCCTGATGTCGCAGCCTATA SEQ ID AGGCCAACAGGGACCT NO: 2272 ABCB1 NM_000927.2 AAACACCACTGGAGCATTGACTACCAGGCTCGCCAATGATGCTGCTCAAGTTAAAGGGGCT SEQ ID ATAGGTTCCAGGCTTG NO: 2273 ABCC5 NM_005688.1 TGCAGACTGTACCATGCTGACCATTGCCCATCGCCTGCACACGGTTCTAGGCTCCGATAGGA SEQ ID TTATGGTGCTGGCC NO: 2274 ABCC6 NM_001171.2 GGATGAACCTCGACCTGCTGCAGGAGCACTCGGACGAGGCTATCTGGGCAGCCCTGGAGAC SEQ ID GGTGCAGCTC NO: 2275 ACP1 NM_004300.2 GCTACCAAGTCCGTGCTGTTTGTGTGTCTGGGTAACATTTGTCGATCACCCATTGCAGAAGC SEQ ID AGTTTTC NO: 2276 ADAM10 NM_001110.1 CCCATCAACTTGTGCCAGTACAGGGTCTGTGCAGTGGAGTAGGCACTTCAGTGGTCGAACCA SEQ ID TCACC NO: 2277 ADAM17 NM_003183.3 GAAGTGCCAGGAGGCGATTAATGCTACTTGCAAAGGCGTGTCCTACTGCACAGGTAATAGC SEQ ID AGTGAGTGCCCG NO: 2278 ADAMTS12 NM_030955.2 GGAGAAGGGTGGAGTGCAGCACCCAGATGGATTCTGACTGTGCGGCCATCCAGAGACCTGA SEQ ID CCCTG NO: 2279 ADPRT NM_001618.2 TTGACAACCTGCTGGACATCGAGGTGGCCTACAGTCTGCTCAGGGGAGGGTCTGATGATAGC SEQ ID AGCAAGGATCCCAT NO: 2280 AGXT NM_000030.1 CTTTTCCCTCCAGTGGCACCTCCTGGAAACAGTCCACTTGGGCGCAAAACCCAGTGCCTTCC SEQ ID AAAT NO: 2281 AKAP12 NM_005100.2 TAGAGAGCCCCTGACAATCCTGAGGCTTCATCAGGAGCTAGAGCCATTTAACATTTCCTCTT SEQ ID TCCAAGACCAACC NO: 2282 AKT1 NM_005163.1 CGCTTCTATGGCGCTGAGATTGTGTCAGCCCTGGACTACCTGCACTCGGAGAAGAACGTGGT SEQ ID GTACCGGGA NO: 2283 AKT2 NM_001626.2 TCCTGCCACCCTTCAAACCTCAGGTCACGTCCGAGGTCGACACAAGGTACTTCGATGATGAA SEQ ID TTTACCGCC NO: 2284 AKT3 NM_005465.1 TTGTCTCTGCCTTGGACTATCTACATTCCGGAAAGATTGTGTACCGTGATCTCAAGTTGGAGA SEQ ID ATCTAATGCTGG NO: 2285 AL137428 AL137428.1 CAAGAAGAGGCTCTACCCTGGGACTGGGAATTTCCAAGGCCACCTTTGAGGATCGCAGAGC SEQ ID TCATTT NO: 2286 ALCAM NM_001627.1 GAGGAATATGGAATCCAAGGGGGCCAGTTCCTGCCGTCTGCTCTTCTGCCTCTTGATCTCCG SEQ ID CCAC NO: 2287 ALDH1A1 NM_000689.1 GAAGGAGATAAGGAGGATGTTGACAAGGCAGTGAAGGCCGCAAGACAGGCTTTTCAGATTG SEQ ID GATCTCCGTGGCG NO: 2288 ALDOA NM_000034.2 GCCTGTACGTGCCAGCTCCCCGACTGCCAGAGCCTCAACTGTCTCTGCTTCGAGATCAAGCT SEQ ID CCGATGA NO: 2289 AMFR NM_001144.2 GATGGTTCAGCTCTGCAAGGATCGATTTGAATATCTTTCCTTCTCGCCCACCACGCCGATGA SEQ ID GCAGCCACGGTCGA NO: 2290 ANGPT2 NM_001147.1 CCGTGAAAGCTGCTCTGTAAAAGCTGACACAGCCCTCCCAAGTGAGCAGGACTGTTCTTCCC SEQ ID ACTGCAA NO: 2291 ANTXR1 NM_032208.1 CTCCAGGTGTACCTCCAACCCTAGCCTTCTCCCACAGCTGCCTACAACAGAGTCTCCCAGCC SEQ ID TTCTC NO: 2292 ANXA1 NM_000700.1 GCCCCTATCCTACCTTCAATCCATCCTCGGATGTCGCTGCCTTGCATAAGGCCATAATGGTTA SEQ ID AAGG NO: 2293 ANXA2 NM_004039.1 CAAGACACTAAGGGCGACTACCAGAAAGCGCTGCTGTACCTGTGTGGTGGAGATGACTGAA SEQ ID GCCCGACACG NO: 2294 ANXA5 NM_001154.2 GCTCAAGCCTGGAAGATGACGTGGTGGGGGACACTTCAGGGTACTACCAGCGGATGTTGGT SEQ ID GGTTCT NO: 2295 AP-1 (JUN NM_002228.2 GACTGCAAAGATGGAAACGACCTTCTATGACGATGCCCTCAACGCCTCGTTCCTCCCGTCCG SEQ ID official) AGAGCGGACCTTATGGCTA NO: 2296 APC NM_000038.1 GGACAGCAGGAATGTGTTTCTCCATACAGGTCACGGGGAGCCAATGGTTCAGAAACAAATC SEQ ID GAGTGGGT NO: 2297 APEX-1 NM_001641.2 GATGAAGCCTTTCGCAAGTTCCTGAAGGGCCTGGCTTCCCGAAAGCCCCTTGTGCTGTGTGG SEQ ID AGACCT NO: 2298 APG-1 NM_014278.2 ACCCCGGCCTGTATATCATTGGGATCAAGAACTCGAGCCATTGGAAATGCAGCAAAGAGCC SEQ ID AGATAG NO: 2299 APN NM_001150.1 CCACCTTGGACCAAAGTAAAGCGTGGAATCGTTACCGCCTCCCCAACACGCTGAAACCCGAT SEQ ID (ANPEP TCCTACCAGGTGACGCTGAGA NO: official) 2300 APOC1 NM_001645.3 GGAAACACACTGGAGGACAAGGCTCGGGAACTCATCAGCCGCATCAAACAGAGTGAACTTT SEQ ID CTGCCAAGATGCG NO: 2301 AREG NM_001657.1 TGTGAGTGAAATGCCTTCTAGTAGTGAACCGTCCTCGGGAGCCGACTATGACTACTCAGAAG SEQ ID AGTATGATAACGAACCACAA NO: 2302 ARG NM_005158.2 CGCAGTGCAGCTGAGTATCTGCTCAGCAGTCTAATCAATGGCAGCTTCCTGGTGCGAGAAAG SEQ ID TGAGAGTAGCCCTGGGCA NO: 2303 ARHF NM_019034.2 ACTGGCCCACTTAGTCCTCAAGCTCCCAACCTGCTGTCCCTCAAGCCCCGCTTCTACCAGCCT SEQ ID GTGGAGTTCAG NO: 2304 ATOH1 NM_005172.1 GCAGCCACCTGCAACTTTGCAGGCGAGAGAGCATCCCGTCTACCCGCCTGAGCTGTCCCTCC SEQ ID TGGA NO: 2305 ATP5A1 NM_004046.3 GATGCTGCCACTCAACAACTTTTGAGTCGTGGCGTGCGTCTAACTGAGTTGCTGAAGCAAGG SEQ ID ACA NO: 2306 ATP5E NM_006886.2 CCGCTTTCGCTACAGCATGGTGGCCTACTGGAGACAGGCTGGACTCAGCTACATCCGATACT SEQ ID CCCA NO: 2307 AURKB NM_004217.1 AGCTGCAGAAGAGCTGCACATTTGACGAGCAGCGAACAGCCACGATCATGGAGGAGTTGGC SEQ ID AGATGC NO: 2308 Axin 2 NM_004655.2 GGCTATGTCTTTGCACCAGCCACCAGCGCCAACGACAGTGAGATATCCAGTGATGCGCTGAC SEQ ID GGAT NO: 2309 axin1 NM_003502.2 CCGTGTGACAGCATCGTTGTGGCGTACTACTTCTGCGGGGAACCCATCCCCTACCGCACCCT SEQ ID GGTGAG NO: 2310 B-Catenin NM_001904.1 GGCTCTTGTGCGTACTGTCCTTCGGGCTGGTGACAGGGAAGACATCACTGAGCCTGCCATCT SEQ ID GTGCTCTTCGTCATCTGA NO: 2311 BAD NM_032989.1 GGGTCAGGTGCCTCGAGATCGGGCTTGGGCCCAGAGCATGTTCCAGATCCCAGAGTTTGAGC SEQ ID CGAGTGAGCAG NO: 2312 BAG1 NM_004323.2 CGTTGTCAGCACTTGGAATACAAGATGGTTGCCGGGTCATGTTAATTGGGAAAAAGAACAG SEQ ID TCCACAGGAAGAGGTTGAAC NO: 2313 BAG2 NM_004282.2 CTAGGGGCAAAAAGCATGACTGCTTTTTCCTGTCTGGCATGGAATCACGCAGTCACCTTGGG SEQ ID CATTTAG NO: 2314 BAG3 NM_004281.2 GAAAGTAAGCCAGGCCCAGTTGGACCAGAACTCCCTCCTGGACACATCCCAATTCAAGTGA SEQ ID TCCGCAAAGAGGT NO: 2315 Bak NM_001188.1 CCATTCCCACCATTCTACCTGAGGCCAGGACGTCTGGGGTGTGGGGATTGGTGGGTCTATGT SEQ ID TCCC NO: 2316 Bax NM_004324.1 CCGCCGTGGACACAGACTCCCCCCGAGAGGTCTTTTTCCGAGTGGCAGCTGACATGTTTTCT SEQ ID GACGGCAA NO: 2317 BBC3 NM_014417.1 CCTGGAGGGTCCTGTACAATCTCATCATGGGACTCCTGCCCTTACCCAGGGGCCACAGAGCC SEQ ID CCCGAGATGGAGCCCAATTAG NO: 2318 BCAS1 NM_003657.1 CCCCGAGACAACGGAGATAAGTGCTGTTGCGGATGCCAACGGAAAGAATCTTGGGAAAGAG SEQ ID GCCAAACCCGAG NO: 2319 Bcl2 NM_000633.1 CAGATGGACCTAGTACCCACTGAGATTTCCACGCCGAAGGACAGCGATGGGAAAAATGCCC SEQ ID TTAAATCATAGG NO: 2320 BCL2L10 NM_020396.2 GCTGGGATGGCTTTTGTCACTTCTTCAGGACCCCCTTTCCACTGGCTTTTTGGAGAAAACAGC SEQ ID TGGTCCAGGC NO: 2321 BCL2L11 NM_138621.1 AATTACCAAGCAGCCGAAGACCACCCACGAATGGTTATCTTACGACTGTTACGTTACATTGT SEQ ID CCGCCTG NO: 2322 BCL2L12 NM_138639.1 AACCCACCCCTGTCTTGGAGCTCCGGGTAGCTCTCAAACTCGAGGCTGCGCACCCCCTTTCC SEQ ID CGTCAGCTGAG NO: 2323 Bclx NM_001191.1 CTTTTGTGGAACTCTATGGGAACAATGCAGCAGCCGAGAGCCGAAAGGGCCAGGAACGCTT SEQ ID CAACCGCTG NO: 2324 BCRP NM_004827.1 TGTACTGGCGAAGAATATTTGGTAAAGCAGGGCATCGATCTCTCACCCTGGGGCTTGTGGAA SEQ ID GAATCACGTGGC NO: 2325 BFGF NM_007083.1 CCAGGAAGAATGCTTAAGATGTGAGTGGATGGATCTCAATGACCTGGCGAAGACTGAAAAT SEQ ID ACAACTCCCATCACCA NO: 2326 BGN NM_001711.3 GAGCTCCGCAAGGATGACTTCAAGGGTCTCCAGCACCTCTACGCCCTCGTCCTGGTGAACAA SEQ ID CAAG NO: 2327 BID NM_001196.2 GGACTGTGAGGTCAACAACGGTTCCAGCCTCAGGGATGAGTGCATCACAAACCTACTGGTG SEQ ID TTTGGCTTCC NO: 2328 BIK NM_001197.3 ATTCCTATGGCTCTGCAATTGTCACCGGTTAACTGTGGCCTGTGCCCAGGAAGAGCCATTCA SEQ ID CTCCTGCC NO: 2329 BIN1 NM_004305.1 CCTGCAAAAGGGAACAAGAGCCCTTCGCCTCCAGATGGCTCCCCTGCCGCCACCCCCGAGAT SEQ ID CAGAGTCAACCACG NO: 2330 BLMH NM_000386.2 GGTTGCTGCCTCCATCAAAGATGGAGAGGCTGTGTGGTTTGGCTGTGATGTTGGAAAACACT SEQ ID TCAATAGCAAGCTGG NO: 2331 BMP2 NM_001200.1 ATGTGGACGCTCTTTCAATGGACGTGTCCCCGCGTGCTTCTTAGACGGACTGCGGTCTCCTA SEQ ID AAGGTCGACCATGGT NO: 2332 BMP4 NM_001202.2 GGGCTAGCCATTGAGGTGACTCACCTCCATCAGACTCGGACCCACCAGGGCCAGCATGTCA SEQ ID GGATTAGC NO: 2333 BMP7 NM_001719.1 TCGTGGAACATGACAAGGAATTCTTCCACCCACGCTACCACCATCGAGAGTTCCGGTTTGAT SEQ ID CTTTCCA NO: 2334 BMPR1A NM_004329.2 TTGGTTCAGCGAACTATTGCCAAACAGATTCAGATGGTCCGGCAAGTTGGTAAAGGCCGATA SEQ ID TGGAGA NO: 2335 BRAF NM_004333.1 CCTTCCGACCAGCAGATGAAGATCATCGAAATCAATTTGGGCAACGAGACCGATCCTCATCA SEQ ID GCTCCCAATGTGCATATAAA NO: 2336 BRCA1 NM_007295.1 TCAGGGGGCTAGAAATCTGTTGCTATGGGCCCTTCACCAACATGCCCACAGATCAACTGGAA SEQ ID TGG NO: 2337 BRCA2 NM_000059.1 AGTTCGTGCTTTGCAAGATGGTGCAGAGCTTTATGAAGCAGTGAAGAATGCAGCAGACCCA SEQ ID GCTTACCTT NO: 2338 BRK NM_005975.1 GTGCAGGAAAGGTTCACAAATGTGGAGTGTCTGCGTCCAATACACGCGTGTGCTCCTCTCCT SEQ ID TACTCCATCGTGTGTGC NO: 2339 BTF3 NM_001207.2 CAGTGATCCACTTTAACAACCCTAAAGTTCAGGCATCTCTGGCAGCGAACACTTTCACCATT SEQ ID ACAGGCCATGCT NO: 2340 BTRC NM_033637.2 GTTGGGACACAGTTGGTCTGCAGTCGGCCCAGGACGGTCTACTCAGCACAACTGACTGCTTCA SEQ ID NO: 2341 BUB1 NM_004336.1 CCGAGGTTAATCCAGCACGTATGGGGCCAAGTGTAGGCTCCCAGCAGGAACTGAGAGCGCC SEQ ID ATGTCTT NO: 2342 BUB1B NM_001211.3 TCAACAGAAGGCTGAACCACTAGAAAGACTACAGTCCCAGCACCGACAATTCCAAGCTCGA SEQ ID GTGTCTCGGCAAACTCTGTTG NO: 2343 BUB3 NM_004725.1 CTGAAGCAGATGGTTCATCATTTCCTGGGCTGTTAAACAAAGCGAGGTTAAGGTTAGACTCT SEQ ID TGGGAATCAGC NO: 2344 c-abl NM_005157.2 CCATCTCGCTGAGATACGAAGGGAGGGTGTACCATTACAGGATCAACACTGCTTCTGATGGC SEQ ID AAGCTCTACGTCT NO: 2345 c-kit NM_000222.1 GAGGCAACTGCTTATGGCTTAATTAAGTCAGATGCGGCCATGACTGTCGCTGTAAAGATGCT SEQ ID CAAGCCGAGTGCC NO: 2346 c-myb (MYB NM_005375.1 AACTCAGACTTGGAAATGCCTTCTTTAACTTCCACCCCCCTCATTGGTCACAAATTGACTGTT SEQ ID official) ACAACACCATTTCATAGAGACCAG NO: 2347 c-Src NM_005417.3 TGAGGAGTGGTATTTTGGCAAGATCACCAGACGGGAGTCAGAGCGGTTACTGCTCAATGCA SEQ ID GAGAACCCGAGAG NO: 2348 C20 orf1 NM_012112.2 TCAGCTGTGAGCTGCGGATACCGCCCGGCAATGGGACCTGCTCTTAACCTCAAACCTAGGAC SEQ ID CGT NO: 2349 C20ORF126 NM_030815.2 CCAGCACTGCTCGTTACTGTCTGCCTTCAGTGGTCTGAGGTCCCAGTATGAACTGCCGTGAA SEQ ID GTCAA NO: 2350 C8orf4 NM_020130.2 CTACGAGTCAGCCCATCCATCCATGGCTACCACTTCGACACAGCCTCTCGTAAGAAAGCCGT SEQ ID GGGCA NO: 2351 CA9 NM_001216.1 ATCCTAGCCCTGGTTTTTGGCCTCCTTTTTGCTGTCACCAGCGTCGCGTTCCTTGTGCAGATG SEQ ID AGAAGGCAG NO: 2352 Cad17 NM_004063.2 GAAGGCCAAGAACCGAGTCAAATTATATTCCAGTTTAAGGCCAATCCTCCTGCTGTGACTTT SEQ ID TGAACTAACTGGGGA NO: 2353 CALD1 NM_004342.4 CACTAAGGTTTGAGACAGTTCCAGAAAGAACCCAAGCTCAAGACGCAGGACGAGCTCAGTT SEQ ID GTAGAGGGCTAATTCGC NO: 2354 CAPG NM_001747.1 GATTGTCACTGATGGGGAGGAGCCTGCTGAGATGATCCAGGTCCTGGGCCCCAAGCCTGCTC SEQ ID TGAAGG NO: 2355 CAPN1 NM_005186.2 CAAGAAGCTGTACGAGCTCATCATCACCCGCTACTCGGAGCCCGACCTGGCGGTCGACTTTG SEQ ID ACAATTTCGTTTGCTGC NO: 2356 CASP8 NM_033357.1 CCTCGGGGATACTGTCTGATCATCAACAATCACAATTTTGCAAAAGCACGGGAGAAAGTGC SEQ ID CCAAACTTC NO: 2357 CASP9 NM_001229.2 TGAATGCCGTGGATTGCACGTGGCCTCTTGAGCAGTGGCTGGTCCAGGGCTAGTGACTTGTG SEQ ID TCCCATGATCCCTGT NO: 2358 CAT NM_001752.1 ATCCATTCGATCTCACCAAGGTTTGGCCTCACAAGGACTACCCTCTCATCCCAGTTGGTAAA SEQ ID CTGGTCTTAAACCGGA NO: 2359 CAV1 NM_001753.3 GTGGCTCAACATTGTGTTCCCATTTCAGCTGATCAGTGGGCCTCCAAGGAGGGGCTGTAAAA SEQ ID TGGAGGCCATTG NO: 2360 CBL NM_005188.1 TCATTCACAAACCTGGCAGTTATATCTTCCGGCTGAGCTGTACTCGTCTGGGTCAGTGGGCT SEQ ID ATTGGGTATG NO: 2361 CCL20 NM_004591.1 CCATGTGCTGTACCAAGAGTTTGCTCCTGGCTGCTTTGATGTCAGTGCTGCTACTCCACCTCT SEQ ID GCGGCG NO: 2362 CCL3 NM_002983.1 AGCAGACAGTGGTCAGTCCTTTCTTGGCTCTGCTGACACTCGAGCCCACATTCCGTCACCTG SEQ ID CTCAGAATCATGCAG NO: 2363 CCNA2 NM_001237.2 CCATACCTCAAGTATTTGCCATCAGTTATTGCTGGAGCTGCCTTTCATTTAGCACTCTACACA SEQ ID GTCACGGGACAAAGCT NO: 2364 CCNB1 NM_031966.1 TTCAGGTTGTTGCAGGAGACCATGTACATGACTGTCTCCATTATTGATCGGTTCATGCAGAA SEQ ID TAATTGTGTGCCCAAGAAGATG NO: 2365 CCNB2 NM_004701.2 AGGCTTCTGCAGGAGACTCTGTACATGTGCGTTGGCATTATGGATCGATTTTTACAGGTTCA SEQ ID GCCAGTTTCCC NO: 2366 CCND1 NM_001758.1 GCATGTTCGTGGCCTCTAAGATGAAGGAGACCATCCCCCTGACGGCCGAGAAGCTGTGCATC SEQ ID TACACCG NO: 2367 CCND3 NM_001760.2 CCTCTGTGCTACAGATTATACCTTTGCCATGTACCCGCCATCCATGATCGCCACGGGCAGCA SEQ ID TTGGGGCTGCAGTG NO: 2368 CCNE1 NM_001238.1 AAAGAAGATGATGACCGGGTTTACCCAAACTCAACGTGCAAGCCTCGGATTATTGCACCATC SEQ ID CAGAGGCTC NO: 2369 CCNE2 NM_057749.1 ATGCTGTGGCTCCTTCCTAACTGGGGCTTTCTTGACATGTAGGTTGCTTGGTAATAACCTTTT SEQ ID TGTATATCACAATTTGGGT NO: 2370 CCNE2 NM_057749var1 GGTCACCAAGAAACATCAGTATGAAATTAGGAATTGTTGGCCACCTGTATTATCTGGGGGGA SEQ ID variant 1 TCAGTCCTTGCATTATCATTGAA NO: 2371 CCR7 NM_001838.2 GGATGACATGCACTCAGCTCTTGGCTCCACTGGGATGGGAGGAGAGGACAAGGGAAATGTC SEQ ID AGG NO: 2372 CD105 NM_000118.1 GCAGGTGTCAGCAAGTATGATCAGCAATGAGGCGGTGGTCAATATCCTGTCGAGCTCATCAC SEQ ID CACAGCGGAAAAA NO: 2373 CD134 NM_003327.1 GCCCAGTGCGGAGAACAGGTCCAGCTTGATTCTCGTCTCTGCACTTAAGCTGTTCTCCAGGT SEQ ID (TNFRSF4 GCGTGTGATT NO: official) 2374 CD18 NM_000211.1 CGTCAGGACCCACCATGTCTGCCCCATCACGCGGCCGAGACATGGCTTGGCCACAGCTCTTG SEQ ID AGGATGTCACCAATTAACC NO: 2375 CD24 NM_013230.1 TCCAACTAATGCCACCACCAAGGCGGCTGGTGGTGCCCTGCAGTCAACAGCCAGTCTCTTCG SEQ ID TGGTCTCACTCTCTC NO: 2376 CD28 NM_006139.1 TGTGAAAGGGAAACACCTTTGTCCAAGTCCCCTATTTCCCGGACCTTCTAAGCCCTTTTGGGT SEQ ID GCT NO: 2377 CD31 NM_000442.1 TGTATTTCAAGACCTCTGTGCACTTATTTATGAACCTGCCCTGCTCCCACAGAACACAGCAAT SEQ ID TCCTCAGGCTAA NO: 2378 CD34 NM_001773.1 CCACTGCACACACCTCAGAGGCTGTTCTTGGGGCCCTACACCTTGAGGAGGGGCAGGTAAA SEQ ID CTCCTG NO: 2379 CD3z NM_000734.1 AGATGAAGTGGAAGGCGCTTTTCACCGCGGCCATCCTGCAGGCACAGTTGCCGATTACAGA SEQ ID GGCA NO: 2380 CD44E X55150 ATCACCGACAGCACAGACAGAATCCCTGCTACCAATATGGACTCCAGTCATAGTACAACGCT SEQ ID TCAGCCTACTGCAAATCCAAACACAGGT NO: 2381 CD44s M59040.1 GACGAAGACAGTCCCTGGATCACCGACAGCACAGACAGAATCCCTGCTACCAGAGACCAAG SEQ ID ACACATTCCACCCCAGT NO: 2382 CD44v3 AJ251595v3 CACACAAAACAGAACCAGGACTGGACCCAGTGGAACCCAAGCCATTCAAATCCGGAAGTGC SEQ ID TACTTCAG NO: 2383 CD44v6 AJ251595v6 CTCATACCAGCCATCCAATGCAAGGAAGGACAACACCAAGCCCAGAGGACAGTTCCTGGAC SEQ ID TGATTTCTTCAACCCAA NO: 2384 CD68 NM_001251.1 TGGTTCCCAGCCCTGTGTCCACCTCCAAGCCCAGATTCAGATTCGAGTCATGTACACAACCC SEQ ID AGGGTGGAGGAG NO: 2385 CD80 NM_005191.2 TTCAGTTGCTTTGCAGGAAGTGTCTAGAGGAATATGGTGGGCACAGAAGTAGCTCTGGTGAC SEQ ID CTTGATCAA NO: 2386 CD82 NM_002231.2 GTGCAGGCTCAGGTGAAGTGCTGCGGCTGGGTCAGCTTCTACAACTGGACAGACAACGCTG SEQ ID AGCTCATGAATCGCCCTGAGGTC NO: 2387 CD8A NM_171827.1 AGGGTGAGGTGCTTGAGTCTCCAACGGCAAGGGAACAAGTACTTCTTGATACCTGGGATACT SEQ ID GTGCCC NO: 2388 CD9 NM_001769.1 GGGCGTGGAACAGTTTATCTCAGACATCTGCCCCAAGAAGGACGTACTCGAAACCTTCACCG SEQ ID TG NO: 2389 CDC2 NM_001786.2 GAGAGCGACGCGGTTGTTGTAGCTGCCGCTGCGGCCGCCGCGGAATAATAAGCCGGGATCT SEQ ID ACCATAC NO: 2390 CDC20 NM_001255.1 TGGATTGGAGTTCTGGGAATGTACTGGCCGTGGCACTGGACAACAGTGTGTACCTGTGGAGT SEQ ID GCAAGC NO: 2391 cdc25A NM_001789.1 TCTTGCTGGCTACGCCTCTTCTGTCCCTGTTAGACGTCCTCCGTCCATATCAGAACTGTGCCA SEQ ID CAATGCAG NO: 2392 CDC25B NM_021874.1 AAACGAGCAGTTTGCCATCAGACGCTTCCAGTCTATGCCGGTGAGGCTGCTGGGCCACAGCC SEQ ID CCGTGCTTCGGAACATCACCAAC NO: 2393 CDC25C NM_001790.2 GGTGAGCAGAAGTGGCCTATATCGCTCCCCGTCGATGCCAGAGAACTTGAACAGGCCAAGA SEQ ID CTGAAG NO: 2394 CDC4 NM_018315.2 GCAGTCCGCTGTGTTCAATATGATGGCAGGAGGGTTGTTAGTGGAGCATATGATTTTATGGT SEQ ID AAAGGTGTGGGATCC NO: 2395 CDC42 NM_001791.2 TCCAGAGACTGCTGAAAAGCTGGCCCGTGACCTGAAGGCTGTCAAGTATGTGGAGTGTTCTG SEQ ID CACTTACACA NO: 2396 CDC42BPA NM_003607.2 GAGCTGAAAGACGCACACTGTCAGAGGAAACTGGCCATGCAGGAATTCATGGAGATCAATG SEQ ID AGCGGC NO: 2397 CDC6 NM_001254.2 GCAACACTCCCCATTTACCTCCTTGTTCTCCACCAAAGCAAGGCAAGAAAGAGAATGGTCCC SEQ ID CCTCA NO: 2398 CDCA7 v2 NM_145810.1 AAGACCGTGGATGGCTACATGAATGAAGATGACCTGCCCAGAAGCCGTCGCTCCAGATCAT SEQ ID CCGTGACCCT NO: 2399 CDH1 NM_004360.2 TGAGTGTCCCCCGGTATCTTCCCCGCCCTGCCAATCCCGATGAAATTGGAAATTTTATTGATG SEQ ID AAAATCTGAAAGCGGCTG NO: 2400 CDH11 NM_001797.2 GTCGGCAGAAGCAGGACTTGTACCTTCTGCCCATAGTGATCAGCGATGGCGGCATCCCGCCC SEQ ID ATGAGTAG NO: 2401 CDH3 NM_001793.3 ACCCATGTACCGTCCTCGGCCAGCCAACCCAGATGAAATCGGCAACTTTATAATTGAGAACC SEQ ID TGAAGGCGG NO: 2402 CDK2 NM_001798.2 AATGCTGCACTACGACCCTAACAAGCGGATTTCGGCCAAGGCAGCCCTGGCTCACCCTTTCT SEQ ID TCCAGGATGTGACCAA NO: 2403 CDX1 NM_001804.1 AGCAACACCAGCCTCCTGGCCACCTCCTCTCCAATGCCTGTGAAAGAGGAGTTTCTGCCATA SEQ ID GCCC NO: 2404 Cdx2 NM_001265.2 GGGCAGGCAAGGTTTACACTGCGGAAGCCAAAGGCAGCTAAGATAGAAAGCTGGACTGACC SEQ ID AAAGAC NO: 2405 CEACAM1 NM_001712.2 ACTTGCCTGTTCAGAGCACTCATTCCTTCCCACCCCCAGTCCTGTCCTATCACTCTAATTCGG SEQ ID ATTTGCCA NO: 2406 CEACAM6 NM_002483.2 CACAGCCTCACTTCTAACCTTCTGGAACCCACCCACCACTGCCAAGCTCACTATTGAATCCA SEQ ID CGCCATTCAA NO: 2407 CEBPB NM_005194.2 GCAACCCACGTGTAACTGTCAGCCGGGCCCTGAGTAATCGCTTAAAGATGTTCCTACGGGCT SEQ ID TGT NO: 2408 CEGP1 NM_020974.1 TGACAATCAGCACACCTGCATTCACCGCTCGGAAGAGGGCCTGAGCTGCATGAATAAGGAT SEQ ID CACGGCTGTAGTCACA NO: 2409 CENPA NM_001809.2 TAAATTCACTCGTGGTGTGGACTTCAATTGGCAAGCCCAGGCCCTATTGGCCCTACAAGAGGC SEQ ID NO: 2410 CENPE NM_001813.1 GGATGCTGGTGACCTCTTCTTCCCTCACGTTGCAACAGGAATTAAAGGCTAAAAGAAAACGA SEQ ID AGAGTTACTTGGTGCCTTGGC NO: 2411 CENPF NM_016343.2 CTCCCGTCAACAGCGTTCTTTCCAAACACTGGACCAGGAGTGCATCCAGATGAAGGCCAGAC SEQ ID TCACCC NO: 2412 CES2 NM_003869.4 ACTTTGCGAGAAATGGGAACCCCAATGGCGAGGGTCTGCCACACTGGCCGCTGTTCGACCA SEQ ID GGAGGAGCAATACCTG NO: 2413 CGA NM_001275.2 CTGAAGGAGCTCCAAGACCTCGCTCTCCAAGGCGCCAAGGAGAGGGCACATCAGCAGAAGA SEQ ID (CHGA AACACAGCGGTTTTG NO: official) 2414 CGB NM_000737.2 CCACCATAGGCAGAGGCAGGCCTTCCTACACCCTACTCCCTGTGCCTCCAGCCTCGACTAGT SEQ ID CCCTAGCACTCGACGACT NO: 2415 CHAF1B NM_005441.1 GAGGCCAGTGGTGGAAACAGGTGTGGAGCTGATGAGTCTGCCCTACCGCCTGGTGTTTGCTG SEQ ID TGGCCTCGGA NO: 2416 CHD2 NM_001271.1 CTCTGTGCGAGGCTGTCAGCCACACTAGGTATCAGGGATCCCGAGATGGGTACCAGCCCAC SEQ ID AGTCCTTACC NO: 2417 CHFR NM_018223.1 AAGGAAGTGGTCCCTCTGTGGCAAGTGATGAAGTCTCCAGCTTTGCCTCAGCTCTCCCAGAC SEQ ID AGAAAGACTGCGTC NO: 2418 Chk1 NM_001274.1 GATAAATTGGTACAAGGGATCAGCTTTTCCCAGCCCACATGTCCTGATCATATGCTTTTGAA SEQ ID TAGTCAGTTACTTGGCACCC NO: 2419 Chk2 NM_007194.1 ATGTGGAACCCCCACCTACTTGGCGCCTGAAGTTCTTGTTTCTGTTGGGACTGCTGGGTATAA SEQ ID CCGTGCTGTGGACTG NO: 2420 CIAP1 NM_001166.2 TGCCTGTGGTGGGAAGCTCAGTAACTGGGAACCAAAGGATGATGCTATGTCAGAACACCGG SEQ ID AGGCATTTTCC NO: 2421 cIAP2 NM_001165.2 GGATATTTCCGTGGCTCTTATTCAAACTCTCCATCAAATCCTGTAAACTCCAGAGCAAATCA SEQ ID AGATTTTTCTGCCTTGATGAGAAG NO: 2422 CKS1B NM_001826.1 GGTCCCTAAAACCCATCTGATGTCTGAATCTGAATGGAGGAATCTTGGCGTTCAGCAGAGTC SEQ ID AGGGATGGGTCCATTA NO: 2423 CKS2 NM_001827.1 GGCTGGACGTGGTTTTGTCTGCTGCGCCCGCTCTTCGCGCTCTCGTTTCATTTTCTGCAGCG SEQ ID NO: 2424 Claudin 4 NM_001305.2 GGCTGCTTTGCTGCAACTGTCCACCCCGCACAGACAAGCCTTACTCCGCCAAGTATTCTGCT SEQ ID GCCCGCTCTG NO: 2425 CLDN1 NM_021101.3 TCTGGGAGGTGCCCTACTTTGCTGTTCCTGTCCCCGAAAAACAACCTCTTACCCAACACCAA SEQ ID GGCCCTATCCA NO: 2426 CLDN7 NM_001307.3 GGTCTGCCCTAGTCATCCTGGGAGGTGCACTGCTCTCCTGTTCCTGTCCTGGGAATGAGAGC SEQ ID AAGGCTGGGTAC NO: 2427 CLIC1 NM_001288.3 CGGTACTTGAGCAATGCCTACGCCCGGGAAGAATTCGCTTCCACCTGTCCAGATGATGAGGA SEQ ID GATCGA NO: 2428 CLTC NM_004859.1 ACCGTATGGACAGCCACAGCCTGGCTTTGGGTACAGCATGTGAGATGAAGCGCTGATCCTGT SEQ ID AGTCA NO: 2429 CLU NM_001831.1 CCCCAGGATACCTACCACTACCTGCCCTTCAGCCTGCCCCACCGGAGGCCTCACTTCTTCTTT SEQ ID CCCAAGTCCCGCA NO: 2430 cMet NM_000245.1 GACATTTCCAGTCCTGCAGTCAATGCCTCTCTGCCCCACCCTTTGTTCAGTGTGGCTGGTGCC SEQ ID ACGACAAATGTGTGCGATCGGAG NO: 2431 cMYC NM_002467.1 TCCCTCCACTCGGAAGGACTATCCTGCTGCCAAGAGGGTCAAGTTGGACAGTGTCAGAGTCC SEQ ID TGAGACAGATCAGCAACAACCG NO: 2432 CNN NM_001299.2 TCCACCCTCCTGGCTTTGGCCAGCATGGCGAAGACGAAAGGAAACAAGGTGAACGTGGGAG SEQ ID TGA NO: 2433 COL1A1 NM_000088.2 GTGGCCATCCAGCTGACCTTCCTGCGCCTGATGTCCACCGAGGCCTCCCAGAACATCACCTA SEQ ID CCACTG NO: 2434 COL1A2 NM_000089.2 CAGCCAAGAACTGGTATAGGAGCTCCAAGGACAAGAAACACGTCTGGCTAGGAGAAACTAT SEQ ID CAATGCTGGCAGCCAGTTT NO: 2435 COPS3 NM_003653.2 ATGCCCAGTGTTCCTGACTTCGAAACGCTATTCTCACAGGTTCAGCTCTTCATCAGCACTTGT SEQ ID AATGGGGAG NO: 2436 COX2 NM_000963.1 TCTGCAGAGTTGGAAGCACTCTATGGTGACATCGATGCTGTGGAGCTGTATCCTGCCCTTCT SEQ ID GGTAGAAAAGCCTCGGC NO: 2437 COX3 MITO_COX3 TCGAGTCTCCCTTCACCATTTCCGACGGCATCTACGGCTCAACATTTTTTGTAGCCACAGGCT SEQ ID TCCACGGACTTCACGTC NO: 2438 CP NM_000096.1 CGTGAGTACACAGATGCCTCCTTCACAAATCGAAAGGAGAGAGGCCCTGAAGAAGAGCATC SEQ ID TTGGCATCCTGG NO: 2439 CRBP NM_002899.2 TGGTCTGCAAGCAAGTATTCAAGAAGGTGCAGTGAGGCCCAAGCAGACAACCTTGTCCCAA SEQ ID CCAATCAGC NO: 2440 CREBBP NM_004380.1 TGGGAAGCAGCTGTGTACCATTCCTCGCGATGCTGCCTACTACAGCTATCAGAATAGGTATC SEQ ID ATTTCTGTGAGAAGTGTTTC NO: 2441 CRIP2 NM_001312.1 GTGCTACGCCACCCTGTTCGGACCCAAAGGCGTGAACATCGGGGGCGCGGGCTCCTACATCT SEQ ID ACGAGAAGCCCCTG NO: 2442 cripto NM_003212.1 GGGTCTGTGCCCCATGACACCTGGCTGCCCAAGAAGTGTTCCCTGTGTAAATGCTGGCACGG SEQ ID (TDGF1 TCA NO: official) 2443 CRK(a) NM_016823.2 CTCCCTAACCTCCAGAATGGGCCCATATATGCCAGGGTTATCCAGAAGCGAGTCCCCAATGC SEQ ID CTACGACAAGACA NO: 2444 CRMP1 NM_001313.1 AAGGTTTTTGGATTGCAAGGGGTTTCCAGGGGCATGTATGACGGTCCTGTGTACGAGGTACC SEQ ID AGCTACACCC NO: 2445 CRYAB NM_001885.1 GATGTGATTGAGGTGCATGGAAAACATGAAGAGCGCCAGGATGAACATGGTTTCATCTCCA SEQ ID GGGAGTTC NO: 2446 CSEL1 NM_001316.2 TTACGCAGCTCATGCTCTTGAACGGCTCTTTACTATGCGAGGGCCTAACAATGCCACTCTCTT SEQ ID TACAGCTGC NO: 2447 CSF1 NM_000757.3 TGCAGCGGCTGATTGACAGTCAGATGGAGACCTCGTGCCAAATTACATTTGAGTTTGTAGAC SEQ ID CAGGAACAGTTG NO: 2448 CSK (SRC) NM_004383.1 CCTGAACATGAAGGAGCTGAAGCTGCTGCAGACCATCGGGAAGGGGGAGTTCGGAGACGTG SEQ ID ATG NO: 2449 CTAG1B NM_001327.1 GCTCTCCATCAGCTCCTGTCTCCAGCAGCTTTCCCTGTTGATGTGGATCACGCAGTGCTTTCT SEQ ID GCCCGTGTT NO: 2450 CTGF NM_001901.1 GAGTTCAAGTGCCCTGACGGCGAGGTCATGAAGAAGAACATGATGTTCATCAAGACCTGTG SEQ ID CCTGCCATTACAACT NO: 2451 CTHRC1 NM_138455.2 GCTCACTTCGGCTAAAATGCAGAAATGCATGCTGTCAGCGTTGGTATTTCACATTCAATGGA SEQ ID GCTGA NO: 2452 CTLA4 NM_005214.2 CACTGAGGTCCGGGTGACAGTGCTTCGGCAGGCTGACAGCCAGGTGACTGAAGTCTGTGCG SEQ ID GCAACCTAC NO: 2453 CTNNBIP1 NM_020248.2 GTTTTCCAGGTCGGAGACGGAAGACCGGAGGCAGTAGCTGCAAAGCCCTTGGAACACCCTG SEQ ID GATGCT NO: 2454 CTSB NM_001908.1 GGCCGAGATCTACAAAAACGGCCCCGTGGAGGGAGCTTTCTCTGTGTATTCGGACTTCCTGC SEQ ID NO: 2455 CTSD NM_001909.1 GTACATGATCCCCTGTGAGAAGGTGTCCACCCTGCCCGCGATCACACTGAAGCTGGGAGGC SEQ ID AAAGGCTACAAGCTGTCCC NO: 2456 CTSH NM_004390.1 GCAAGTTCCAACCTGGAAAGGCCATCGGCTTTGTCAAGGATGTAGCCAACATCACAATCTAT SEQ ID GACGAGGAAGCGATG NO: 2457 CTSL NM_001912.1 GGGAGGCTTATCTCACTGAGTGAGCAGAATCTGGTAGACTGCTCTGGGCCTCAAGGCAATG SEQ ID AAGGCTGCAATGG NO: 2458 CTSL2 NM_001333.2 TGTCTCACTGAGCGAGCAGAATCTGGTGGACTGTTCGCGTCCTCAAGGCAATCAGGGCTGCA SEQ ID ATGGT NO: 2459 CUL1 NM_003592.2 ATGCCCTGGTAATGTCTGCATTCAACAATGACGCTGGCTTTGTGGCTGCTCTTGATAAGGCTT SEQ ID GTGGTCGC NO: 2460 CUL4A NM_003589.1 AAGCATCTTCCTGTTCTTGGACCGCACCTATGTGCTGCAGAACTCCACGCTGCCCTCCATCTG SEQ ID GGATATGGGATT NO: 2461 CXCL12 NM_000609.3 GAGCTACAGATGCCCATGCCGATTCTTCGAAAGCCATGTTGCCAGAGCCAACGTCAAGCATC SEQ ID TCAAA NO: 2462 CXCR4 NM_003467.1 TGACCGCTTCTACCCCAATGACTTGTGGGTGGTTGTGTTCCAGTTTCAGCACATCATGGTTGG SEQ ID CCTTATCCT NO: 2463 CYBA NM_000101.1 GGTGCCTACTCCATTGTGGCGGGCGTGTTTGTGTGCCTGCTGGAGTACCCCCGGGGGAAGAG SEQ ID GAAGAAGGGCTCCAC NO: 2464 CYP1B1 NM_000104.2 CCAGCTTTGTGCCTGTCACTATTCCTCATGCCACCACTGCCAACACCTCTGTCTTGGGCTACC SEQ ID ACATTCCC NO: 2465 CYP2C8 NM_000770.2 CCGTGTTCAAGAGGAAGCTCACTGCCTTGTGGAGGAGTTGAGAAAAACCAAGGCTTCACCC SEQ ID TGTGATCCCACT NO: 2466 CYP3A4 NM_017460.3 AGAACAAGGACAACATAGATCCTTACATATACACACCCTTTGGAAGTGGACCCAGAAACTG SEQ ID CATTGGCATGAGGTTTGC NO: 2467 CYR61 NM_001554.3 TGCTCATTCTTGAGGAGCATTAAGGTATTTCGAAACTGCCAAGGGTGCTGGTGCGGATGGAC SEQ ID ACTAATGCAGCCAC NO: 2468 DAPK1 NM_004938.1 CGCTGACATCATGAATGTTCCTCGACCGGCTGGAGGCGAGTTTGGATATGACAAAGACACAT SEQ ID CGTTGCTGAAAGAGA NO: 2469 DCC NM_005215.1 AAATGTCCTCCTCGACTGCTCCGCGGAGTCCGACCGAGGAGTTCCAGTGATCAAGTGGAAG SEQ ID AAAGATGGCATTCA NO: 2470 DCC_exons18-23 X76132_18-23 GGTCACCGTTGGTGTCATCACAGTGCTGGTAGTGGTCATCGTGGCTGTGATTTGCACCCGAC SEQ ID GCTC NO: 2471 DCC_exons6-7 X76132_6-7 ATGGAGATGTGGTCATTCCTAGTGATTATTTTCAGATAGTGGGAGGAAGCAACTTACGGATA SEQ ID CTTGGGGTGGTG NO: 2472 DCK NM_000788.1 GCCGCCACAAGACTAAGGAATGGCCACCCCGCCCAAGAGAAGCTGCCCGTCTTTCTCAGCC SEQ ID AGCTCTGAGGGGACCCGCATCAAGAAAATCTCCATCGAAGGGAACATCG NO: 2473 DDB1 NM_001923.2 TGCGGATCATCCGGAATGGAATTGGAATCCACGAGCATGCCAGCATTGACTTACCAGGCATC SEQ ID AAAGGA NO: 2474 DET1 NM_017996.2 CTTGTGGAGATCACCCAATCAGGTTCTATGCCCGGGACTCGGGCCTGCTCAAGTTTGAGATC SEQ ID CAGGCGGG NO: 2475 DHFR NM_000791.2 TTGCTATAACTAAGTGCTTCTCCAAGACCCCAACTGAGTCCCCAGCACCTGCTACAGTGAGC SEQ ID TGCCATTCCAC NO: 2476 DHPS NM_013407.1 GGGAGAACGGGATCAATAGGATCGGAAACCTGCTGGTGCCCAATGAGAATTACTGCAAGTT SEQ ID TGAGGACTGGCTGATGC NO: 2477 DIABLO NM_019887.1 CACAATGGCGGCTCTGAAGAGTTGGCTGTCGCGCAGCGTAACTTCATTCTTCAGGTACAGAC SEQ ID AGTGTTTGTGT NO: 2478 DIAPH1 NM_005219.2 CAAGCAGTCAAGGAGAACCAGAAGCGGCGGGAGACAGAAGAAAAGATGAGGCGAGCAAA SEQ ID ACT NO: 2479 DICER1 NM_177438.1 TCCAATTCCAGCATCACTGTGGAGAAAAGCTGTTTGTCTCCCCAGCATACTTTATCGCCTTCA SEQ ID CTGCC NO: 2480 DKK1 NM_012242.1 TGACAACTACCAGCCGTACCCGTGCGCAGAGGACGAGGAGTGCGGCACTGATGAGTACTGC SEQ ID GCTAGTCCC NO: 2481 DLC1 NM_006094.3 GATTCAGACGAGGATGAGCCTTGTGCCATCAGTGGCAAATGGACTTTCCAAAGGGACAGCA SEQ ID AGAGGTG NO: 2482 DPYD NM_000110.2 AGGACGCAAGGAGGGTTTGTCACTGGCAGACTCGAGACTGTAGGCACTGCCATGGCCCCTG SEQ ID TGCTCAGTAAGGACTCGGCGGACATC NO: 2483 DR4 NM_003844.1 TGCACAGAGGGTGTGGGTTACACCAATGCTTCCAACAATTTGTTTGCTTGCCTCCCATGTAC SEQ ID AGCTTGTAAATCAGATGAAGA NO: 2484 DR5 NM_003842.2 CTCTGAGACAGTGCTTCGATGACTTTGCAGACTTGGTGCCCTTTGACTCCTGGGAGCCGCTC SEQ ID ATGAGGAAGTTGGGCCTCATGG NO: 2485 DRG1 NM_004147.3 CCTGGATCTCCCAGGTATCATTGAAGGTGCCAAGGATGGGAAAGGTAGAGGTCGTCAAGTC SEQ ID ATTGCA NO: 2486 DSP NM_004415.1 TGGCACTACTGCATGATTGACATAGAGAAGATCAGGGCCATGACAATCGCCAAGCTGAAAA SEQ ID CAATGCGGCAGG NO: 2487 DTYMK NM_012145.1 AAATCGCTGGGAACAAGTGCCGTTAATTAAGGAAAAGTTGAGCCAGGGCGTGACCCTCGTC SEQ ID GTGGACAGATACGCATT NO: 2488 DUSP1 NM_004417.2 AGACATCAGCTCCTGGTTCAACGAGGCCATTGACTTCATAGACTCCATCAAGAATGCTGGAG SEQ ID GAAGGGTGTTTGTC NO: 2489 DUSP2 NM_004418.2 TATCCCTGTGGAGGACAACCAGATGGTGGAGATCAGTGCCTGGTTCCAGGAGGCCATAGGC SEQ ID TTCATTGACTGGGTG NO: 2490 DUT NM_001948.2 ACACATGGAGTGCTTCTGGAACTATCAGCCCACTTGACCACCCAGTTTGTGGAAGCACAGGC SEQ ID AAGAG NO: 2491 DYRK1B NM_004714.1 AGCATGACACGGAGATGAAGTACTATATAGTACACCTGAAGCGGCACTTCATGTTCCGGAA SEQ ID CCACCTGTGCCTGGTATT NO: 2492 E2F1 NM_005225.1 ACTCCCTCTACCCTTGAGCAAGGGCAGGGGTCCCTGAGCTGTTCTTCTGCCCCATACTGAAG SEQ ID GAACTGAGGCCTG NO: 2493 EDN1 NM_001955.1 TGCCACCTGGACATCATTTGGGTCAACACTCCCGAGCACGTTGTTCCGTATGGACTTGGAAG SEQ ID endothelin CCCTAGGTCCA NO: 2494 EFNA1 NM_004428.2 TACATCTCCAAACCCATCCACCAGCATGAAGACCGCTGCTTGAGGTTGAAGGTGACTGTCAG SEQ ID TGGCAA NO: 2495 EFNA3 NM_004952.3 ACTACATCTCCACGCCCACTCACAACCTGCACTGGAAGTGTCTGAGGATGAAGGTGTTCGTC SEQ ID TGCTG NO: 2496 EFNB1 NM_004429.3 GGAGCCCGTATCCTGGAGCTCCCTCAACCCCAAGTTCCTGAGTGGGAAGGGCTTGGTGATCT SEQ ID ATCC NO: 2497 EFNB2 NM_004093.2 TGACATTATCATCCCGCTAAGGACTGCGGACAGCGTCTTCTGCCCTCACTACGAGAAGGTCA SEQ ID GCGGGGACTAC NO: 2498 EFP NM_005082.2 TTGAACAGAGCCTGACCAAGAGGGATGAGTTCGAGTTTCTGGAGAAAGCATCAAAACTGCG SEQ ID AGGAATCTCAACA NO: 2499 EGFR NM_005228.1 TGTCGATGGACTTCCAGAACCACCTGGGCAGCTGCCAAAAGTGTGATCCAAGCTGTCCCAAT SEQ ID NO: 2500 EGLN1 NM_022051.1 TCAATGGCCGGACGAAAGCCATGGTTGCTTGTTATCCGGGCAATGGAACGGGTTATGTACGT SEQ ID CATGTTGATAATCCAAA NO: 2501 EGLN3 NM_022073.2 GCTGGTCCTCTACTGCGGGAGCCGGCTGGGCAAATACTACGTCAAGGAGAGGTCTAAGGCA SEQ ID ATGGTGG NO: 2502 EGR1 NM_001964.2 GTCCCCGCTGCAGATCTCTGACCCGTTCGGATCCTTTCCTCACTCGCCCACCATGGACAACTA SEQ ID CCCTAAGCTGGAG NO: 2503 EGR3 NM_004430.2 CCATGTGGATGAATGAGGTGTCTCCTTTCCATACCCAGTCTCACCTTCTCCCCACCCTACCTC SEQ ID ACCTCTTCTCAGGCA NO: 2504 EI24 NM_004879.2 AAAGTGGTGAATGCCATTTGGTTTCAGGATATAGCTGACCTGGCATTTGAGGTATCAGGGAG SEQ ID GAAGCCTCAC NO: 2505 EIF4E NM_001968.1 GATCTAAGATGGCGACTGTCGAACCGGAAACCACCCCTACTCCTAATCCCCCGACTACAGAA SEQ ID GAGGAGAAAACGGAATCTAA NO: 2506 EIF4EL3 NM_004846.1 AAGCCGCGGTTGAATGTGCCATGACCCTCTCCCTCTCTGGATGGCACCATCATTGAAGCTGG SEQ ID CGTCA NO: 2507 ELAVL1 NM_001419.2 GACAGGAGGCCTCTATCCTGTCCCTCCACCCCACCCTCCACCTCAATCCCCTCCCATCTTCCC SEQ ID CAGACCTACCTCAC NO: 2508 EMP1 NM_001423.1 GCTAGTACTTTGATGCTCCCTTGATGGGGTCCAGAGAGCCTCCCTGCAGCCACCAGACTTGG SEQ ID CCTCCAGCTGTTC NO: 2509 EMR3 NM_032571.2 TGGCCTACCTCTTCACCATCATCAACAGCCTCCAAGGCTTCTTCATCTTCTTGGTCTACTGCC SEQ ID TCCTCA NO: 2510 EMS1 NM_005231.2 GGCAGTGTCACTGAGTCCTTGAAATCCTCCCCTGCCCCGCGGGTCTCTGGATTGGGACGCAC SEQ ID AGTGCA NO: 2511 ENO1 NM_001428.2 CAAGGCCGTGAACGAGAAGTCCTGCAACTGCCTCCTGCTCAAAGTCAACCAGATTGGCTCCG SEQ ID TGACCG NO: 2512 EP300 NM_001429.1 AGCCCCAGCAACTACAGTCTGGGATGCCAAGGCCAGCCATGATGTCAGTGGCCCAGCATGG SEQ ID TCAACCTTTGAACA NO: 2513 EPAS1 NM_001430.3 AAGCCTTGGAGGGTTTCATTGCCGTGGTGACCCAAGATGGCGACATGATCTTTCTGTCAGAA SEQ ID AACATCAGCA NO: 2514 EpCAM NM_002354.1 GGGCCCTCCAGAACAATGATGGGCTTTATGATCCTGACTGCGATGAGAGCGGGCTCTTTAAG SEQ ID GCCAAGCAGTGCA NO: 2515 EPHA2 NM_004431.2 CGCCTGTTCACCAAGATTGACACCATTGCGCCCGATGAGATCACCGTCAGCAGCGACTTCGA SEQ ID GGCACGCCAC NO: 2516 EPHB2 NM_004442.4 CAACCAGGCAGCTCCATCGGCAGTGTCCATCATGCATCAGGTGAGCCGCACCGTGGACAGC SEQ ID ATTAC NO: 2517 EPHB4 NM_004444.3 TGAACGGGGTATCCTCCTTAGCCACGGGGCCCGTCCCATTTGAGCCTGTCAATGTCACCACT SEQ ID GACCGAGAGGTACCT NO: 2518 EphB6 NM_004445.1 ACTGGTCCTCCATCGGCTCCCCAGGAGCTTTGGTTTGAGGTGCAAGGCTCAGCACTCATGCT SEQ ID ACACTGG NO: 2519 EPM2A NM_005670.2 ACTGTGGCACTTAGGGGAGATGACATTTGCTTTGGGCAGAGGCAGCTAGCCAGGACACATTT SEQ ID CCACT NO: 2520 ErbB3 NM_001982.1 CGGTTATGTCATGCCAGATACACACCTCAAAGGTACTCCCTCCTCCCGGGAAGGCACCCTTT SEQ ID CTTCAGTGGGTCTCAGTTC NO: 2521 ERCC1 NM_001983.1 GTCCAGGTGGATGTGAAAGATCCCCAGCAGGCCCTCAAGGAGCTGGCTAAGATGTGTATCC SEQ ID TGGCCG NO: 2522 ERCC2 NM_000400.2 TGGCCTTCTTCACCAGCTACCAGTACATGGAGAGCACCGTGGCCTCCTGGTATGAGCAGGGG SEQ ID ATCCTTG NO: 2523 EREG NM_001432.1 ATAACAAAGTGTAGCTCTGACATGAATGGCTATTGTTTGCATGGACAGTGCATCTATCTGGT SEQ ID GGACATGAGTCAAAACTACTGCAGGTGTG NO: 2524 ERK1 Z11696.1 ACGGATCACAGTGGAGGAAGCGCTGGCTCACCCCTACCTGGAGCAGTACTATGACCCGACG SEQ ID GATGAG NO: 2525 ERK2 NM_002745.1 AGTTCTTGACCCCTGGTCCTGTCTCCAGCCCGTCTTGGCTTATCCACTTTGACTCCTTTGAGC SEQ ID CGTTT NO: 2526 ESPL1 NM_012291.1 ACCCCCAGACCGGATCAGGCAAGCTGGCCCTCATGTCCCCTTCACGGTGTTTGAGGAAGTCT SEQ ID GCCCTACA NO: 2527 EstR1 NM_000125.1 CGTGGTGCCCCTCTATGACCTGCTGCTGGAGATGCTGGACGCCCACCGCCTACATGCGCCCA SEQ ID CTAGCC NO: 2528 ETV4 NM_001986.1 TCCAGTGCCTATGACCCCCCCAGACAAATCGCCATCAAGTCCCCTGCCCCTGGTGCCCTTGG SEQ ID ACAGT NO: 2529 F3 NM_001993.2 GTGAAGGATGTGAAGCAGACGTACTTGGCACGGGTCTTCTCCTACCCGGCAGGGAATGTGG SEQ ID AGAGCACCGGTT NO: 2530 FABP4 NM_001442.1 GCTTTGCCACCAGGAAAGTGGCTGGCATGGCCAAACCTAACATGATCATCAGTGTGAATGG SEQ ID GGATG NO: 2531 FAP NM_004460.2 CTGACCAGAACCACGGCTTATCCGGCCTGTCCACGAACCACTTATACACCCACATGACCCAC SEQ ID TTCC NO: 2532 fas NM_000043.1 GGATTGCTCAACAACCATGCTGGGCATCTGGACCCTCCTACCTCTGGTTCTTACGTCTGTTGC SEQ ID TAGATTATCGTCCAAAAGTGTTAATGCC NO: 2533 fasI NM_000639.1 GCACTTTGGGATTCTTTCCATTATGATTCTTTGTTACAGGCACCGAGAATGTTGTATTCAGTG SEQ ID AGGGTCTTCTTACATGC NO: 2534 FASN NM_004104.4 GCCTCTTCCTGTTCGACGGCTCGCCCACCTACGTACTGGCCTACACCCAGAGCTACCGGGCA SEQ ID AAGC NO: 2535 FBXO5 NM_012177.2 GGCTATTCCTCATTTTCTCTACAAAGTGGCCTCAGTGAACATGAAGAAGGTAGCCTCCTGGA SEQ ID GGAGAATTTCGGTGACAGTCTACAATCC NO: 2536 FBXW7 NM_033632.1 CCCCAGTTTCAACGAGACTTCATTTCATTGCTCCCTAAAGAGTTGGCACTCTATGTGCTTTCA SEQ ID TTCCTGGAAC NO: 2537 FDXR NM_004110.2 GAGATGATTCAGTTACCGGGAGCCCGGCCCATTTTGGATCCTGTGGATTTCTTGGGTCTCCA SEQ ID GGACAAGAT NO: 2538 FES NM_002005.2 CTCTGCAGGCCTAGGTGCAGCTCCTCAGCGGCTCCAGCTCATATGCTGACAGCTCTTCACAG SEQ ID TCCTGG NO: 2539 FGF18 NM_003862.1 CGGTAGTCAAGTCCGGATCAAGGGCAAGGAGACGGAATTCTACCTGTGCATGAACCGCAAA SEQ ID GGCAAGC NO: 2540 FGF2 NM_002006.2 AGATGCAGGAGAGAGGAAGCCTTGCAAACCTGCAGACTGCTTTTTGCCCAATATAGATTGG SEQ ID GTAAGGCTGCAAAAC NO: 2541 FGFR1 NM_023109.1 CACGGGACATTCACCACATCGACTACTATAAAAAGACAACCAACGGCCGACTGCCTGTGAA SEQ ID GTGGATGGCACCC NO: 2542 FGFR2 NM_000141.2 GAGGGACTGTTGGCATGCAGTGCCCTCCCAGAGACCAACGTTCAAGCAGTTGGTAGAAGAC SEQ ID isoform 1 TTGGATCGAATTCTCACTC NO: 2543 FHIT NM_002012.1 CCAGTGGAGCGCTTCCATGACCTGCGTCCTGATGAAGTGGCCGATTTGTTTCAGACGACCCA SEQ ID GAGAG NO: 2544 FIGF NM_004469.2 GGTTCCAGCTTTCTGTAGCTGTAAGCATTGGTGGCCACACCACCTCCTTACAAAGCAACTAG SEQ ID AACCTGCGGC NO: 2545 FLJ12455 NM_022078.1 CCACCAGCATGAAGTTTCGGACAGACATGGCCTTTGTGAGGGGTTCCAGTTGTGCTTCAGAC SEQ ID AGCC NO: 2546 FLJ20712 AK000719.1 GCCACACAAACATGCTCCTGCTCCTGGCGGAGGCAGAGCTGCTGGGAAAGACATTTCGGAA SEQ ID GTTTCCTGTGGC NO: 2547 FLT1 NM_002019.1 GGCTCCCGAATCTATCTTTGACAAAATCTACAGCACCAAGAGCGACGTGTGGTCTTACGGAG SEQ ID TATTGCTGTGGGA NO: 2548 FLT4 NM_002020.1 ACCAAGAAGCTGAGGACCTGTGGCTGAGCCCGCTGACCATGGAAGATCTTGTCTGCTACAG SEQ ID CTTCCAGG NO: 2549 FOS NM_005252.2 CGAGCCCTTTGATGACTTCCTGTTCCCAGCATCATCCAGGCCCAGTGGCTCTGAGACAGCCC SEQ ID GCTCC NO: 2550 FOXO3A NM_001455.1 TGAAGTCCAGGACGATGATGCGCCTCTCTCGCCCATGCTCTACAGCAGCTCAGCCAGCCTGT SEQ ID CACCTTCAGTAAGCAAGCCGT NO: 2551 FPGS NM_004957.3 CAGCCCTGCCAGTTTGACTATGCCGTCTTCTGCCCTAACCTGACAGAGGTGTCATCCACAGG SEQ ID CAAC NO: 2552 FRP1 NM_003012.2 TTGGTACCTGTGGGTTAGCATCAAGTTCTCCCCAGGGTAGAATTCAATCAGAGCTCCAGTTT SEQ ID GCATTTGGATGTG NO: 2553 FST NM_006350.2 GTAAGTCGGATGAGCCTGTCTGTGCCAGTGACAATGCCACTTATGCCAGCGAGTGTGCCATG SEQ ID AAGGAAGCTG NO: 2554 Furin NM_002569.1 AAGTCCTCGATACGCACTATAGCACCGAGAATGACGTGGAGACCATCCGGGCCAGCGTCTG SEQ ID CGCCCCCTGCCACGCCTCATGTGCCACATGCCAG NO: 2555 FUS NM_004960.1 GGATAATTCAGACAACAACACCATCTTTGTGCAAGGCCTGGGTGAGAATGTTACAATTGAGT SEQ ID CTGTGGCTGATTACTTCA NO: 2556 FUT1 NM_000148.1 CCGTGCTCATTGCTAACCACTGTCTGTCCCTGAACTCCCAGAACCACTACATCTGGCTTTGGG SEQ ID CAG NO: 2557 FUT3 NM_000149.1 CAGTTCGGTCCAACAGAGAAAGCAGGCAACCACCATGTCATTTGAAAACAGTTTCATCGGG SEQ ID ATATAATTCGCA NO: 2558 FUT6 NM_000150.1 CGTGTGTCTCAAGACGATCCCACTGTGTACCCTAATGGGTCCCGCTTCCCAGACAGCACAGG SEQ ID GACC NO: 2559 FXYD5 NM_014164.4 AGAGCACCAAAGCAGCTCATCCCACTGATGACACCACGACGCTCTCTGAGAGACCATCCCC SEQ ID AAGCAC NO: 2560 FYN NM_002037.3 GAAGCGCAGATCATGAAGAAGCTGAAGCACGACAAGCTGGTCCAGCTCTATGCAGTGGTGT SEQ ID CTGAGGAG NO: 2561 FZD1 NM_003505.1 GGTGCACCAGTTCTACCCTCTAGTGAAAGTGCAGTGTTCCGCTGAGCTCAAGTTCTTCCTGTG SEQ ID CTCCATGTACGC NO: 2562 FZD2 NM_001466.2 TGGATCCTCACCTGGTCGGTGCTGTGCTGCGCTTCCACCTTCTTCACTGTCACCACGTACTTG SEQ ID GTAGACATGCAGCGC NO: 2563 FZD6 NM_003506.2 AATGAGAGAGGTGAAAGCGGACGGAGCTAGCACCCCCAGGTTAAGAGAACAGGACTGTGG SEQ ID TGAACCT NO: 2564 G-Catenin NM_002230.1 TCAGCAGCAAGGGCATCATGGAGGAGGATGAGGCCTGCGGGCGCCAGTACACGCTCAAGAA SEQ ID AACCACC NO: 2565 G1P2 NM_005101.1 CAACGAATTCCAGGTGTCCCTGAGCAGCTCCATGTCGGTGTCAGAGCTGAAGGCGCAGATC SEQ ID NO: 2566 GADD45 NM_001924.2 GTGCTGGTGACGAATCCACATTCATCTCAATGGAAGGATCCTGCCTTAAGTCAACTTATTTG SEQ ID TTTTTGCCGGG NO: 2567 GADD45B NM_015675.1 ACCCTCGACAAGACCACACTTTGGGACTTGGGAGCTGGGGCTGAAGTTGCTCTGTACCCATG SEQ ID AACTCCCA NO: 2568 GADD45G NM_006705.2 CGCGCTGCAGATCCATTTTACGCTGATCCAGGCTTTCTGCTGCGAGAACGACATCGACATAG SEQ ID TGCG NO: 2569 GAGE4 NM_001474.1 GGAACAGGGTCACCCACAGACTGGGTGTGAGTGTGAAGATGGTCCTGATGGGCAGGAGATG SEQ ID GACCCGCCAAATC NO: 2570 GBP1 NM_002053.1 TTGGGAAATATTTGGGCATTGGTCTGGCCAAGTCTACAATGTCCCAATATCAAGGACAACCA SEQ ID CCCTAGCTTCT NO: 2571 GBP2 NM_004120.2 GCATGGGAACCATCAACCAGCAGGCCATGGACCAACTTCACTATGTGACAGAGCTGACAGA SEQ ID TCGAATCAAGGCAAACTCCTCA NO: 2572 GCLC NM_001498.1 CTGTTGCAGGAAGGCATTGATCATCTCCTGGCCCAGCATGTTGCTCATCTCTTTATTAGAGAC SEQ ID CCACTGAC NO: 2573 GCLM NM_002061.1 TGTAGAATCAAACTCTTCATCATCAACTAGAAGTGCAGTTGACATGGCCTGTTCAGTCCTTG SEQ ID GAGTTGCACAGCTGGATTCTGTG NO: 2574 GCNT1 NM_001490.3 TGGTGCTTGGAGCATAGAAGACTGCCCTTCACAAAGGAAATCCCTGATTATTGTTTGAAATG SEQ ID CTGAGGACGTTGC NO: 2575 GDF15 NM_004864.1 CGCTCCAGACCTATGATGACTTGTTAGCCAAAGACTGCCACTGCATATGAGCAGTCCTGGTC SEQ ID CTTCCACTGT NO: 2576 GIT1 NM_014030.2 GTGTATGACGAGGTGGATCGAAGAGAAAATGATGCAGTGTGGCTGGCTACCCAAAACCACA SEQ ID GCACTCTGGT NO: 2577 GJA1 NM_000165.2 GTTCACTGGGGGTGTATGGGGTAGATGGGTGGAGAGGGAGGGGATAAGAGAGGTGCATGTT SEQ ID GGTATTT NO: 2578 GJB2 NM_004004.3 TGTCATGTACGACGGCTTCTCCATGCAGCGGCTGGTGAAGTGCAACGCCTGGCCTTGTCCCA SEQ ID ACACTGTGGACT NO: 2579 GPX1 NM_000581.2 GCTTATGACCGACCCCAAGCTCATCACCTGGTCTCCGGTGTGTCGCAACGATGTTGCCTGGA SEQ ID ACTTT NO: 2580 GPX2 NM_002083.1 CACACAGATCTCCTACTCCATCCAGTCCTGAGGAGCCTTAGGATGCAGCATGCCTTCAGGAG SEQ ID ACACTGCTGGACC NO: 2581 Grb10 NM_005311.2 CTTCGCCTTTGCTGATTGCCTCTCCAAACGCCTGCCTGACGACTGCCTTGGAGCATGTGCGTT SEQ ID ATGG NO: 2582 GRB14 NM_004490.1 TCCCACTGAAGCCCTTTCAGTTGCGGTTGAAGAAGGACTCGCTTGGAGGAAAAAAGGATGTT SEQ ID TACGCCTGGGCACT NO: 2583 GRB2 NM_002086.2 GTCCATCAGTGCATGACGTTTAAGGCCACGTATAGTCCTAGCTGACGCCAATAATAAAAAAC SEQ ID AAGAAACCAAGTGGGCT NO: 2584 GRB7 NM_005310.1 CCATCTGCATCCATCTTGTTTGGGCTCCCCACCCTTGAGAAGTGCCTCAGATAATACCCTGGT SEQ ID GGCC NO: 2585 GRIK1 NM_000830.2 GTTGGGTGCATCTCTCGGGCGTCCGGCAGCGGCTGTATCTCGGCATGAATTAAGAAGCTAGG SEQ ID AAGATGGAGCACG NO: 2586 GRO1 NM_001511.1 CGAAAAGATGCTGAACAGTGACAAATCCAACTGACCAGAAGGGAGGAGGAAGCTCACTGG SEQ ID TGGCTGTTCCTGA NO: 2587 GRP NM_002091.1 CTGGGTCTCATAGAAGCAAAGGAGAACAGAAACCACCAGCCACCTCAACCCAAGGCCTTGG SEQ ID GCAATCAGCAGCCTTCGTGG NO: 2588 GRPR NM_005314.1 ATGCTGCTGGCCATTCCAGAGGCCGTGTTTTCTGACCTCCATCCCTTCCATGAGGAAAGCAC SEQ ID CAACCAGACCT NO: 2589 GSK3B NM_002093.2 GACAAGGACGGCAGCAAGGTGACAACAGTGGTGGCAACTCCTGGGCAGGGTCCAGACAGG SEQ ID CCACAA NO: 2590 GSTA3 NM_000847.3 TCTCCAACTTCCCTCTGCTGAAGGCCCTGAAAACCAGAATCAGCAACCTGCCCACGGTGAAG SEQ ID AAGT NO: 2591 GSTM1 NM_000561.1 AAGCTATGAGGAAAAGAAGTACACGATGGGGGACGCTCCTGATTATGACAGAAGCCAGTGG SEQ ID CTGAATGAAAAATTCAAGCTGGGCC NO: 2592 GSTM3 NM_000849.3 CAATGCCATCTTGCGCTACATCGCTCGCAAGCACAACATGTGTGGTGAGACTGAAGAAGAA SEQ ID AAGATTCGAGTGGAC NO: 2593 GSTp NM_000852.2 GAGACCCTGCTGTCCCAGAACCAGGGAGGCAAGACCTTCATTGTGGGAGACCAGATCTCCTT SEQ ID CGCTGACTACAACC NO: 2594 GSTT1 NM_000853.1 CACCATCCCCACCCTGTCTTCCACAGCCGCCTGAAAGCCACAATGAGAATGATGCACACTGA SEQ ID GGCC NO: 2595 H2AFZ NM_002106.2 CCGGAAAGGCCAAGACAAAGGCGGTTTCCCGCTCGCAGAGAGCCGGCTTGCAGTTCCCAGT SEQ ID GGGCCGTATT NO: 2596 HB-EGF NM_001945.1 GACTCCTTCGTCCCCAGTTGCCGTCTAGGATTGGGCCTCCCATAATTGCTTTGCCAAAATACC SEQ ID AGAGCCTTCAAGTGCCA NO: 2597 hCRA a U78556.1 TGACACCCTTACCTTCCTGAGAAATACCCCCTGGGAGCGCGGAAAGCAGAGCGGACAGGTC SEQ ID AGTGACTTCTATTTTTGACTCGTGTTTTT NO: 2598 HDAC1 NM_004964.2 CAAGTACCACAGCGATGACTACATTAAATTCTTGCGCTCCATCCGTCCAGATAACATGTCGG SEQ ID AGTACAGCAAGC NO: 2599 HDAC2 NM_001527.1 GGTGGCTACACAATCCGTAATGTTGCTCGATGTTGGACATATGAGACTGCAGTTGCCCTTGA SEQ ID TTGTGAGATTCCCA NO: 2600 HDGF NM_004494.1 TCCTAGGCATTCTGGACCTCTGGGTTGGGATCAGGGGTAGGAATGGAAGGATGGAGCATCA SEQ ID ACAGC NO: 2601 hENT1 NM_004955.1 AGCCGTGACTGTTGAGGTCAAGTCCAGCATCGCAGGCAGCAGCACCTGGGAACGTTACTT SEQ ID NO: 2602 Hepsin NM_002151.1 AGGCTGCTGGAGGTCATCTCCGTGTGTGATTGCCCCAGAGGCCGTTTCTTGGCCGCCATCTG SEQ ID CCAAGACTGTGGCCGCAGGAAG NO: 2603 HER2 NM_004448.1 CGGTGTGAGAAGTGCAGCAAGCCCTGTGCCCGAGTGTGCTATGGTCTGGGCATGGAGCACTT SEQ ID GCGAGAGG NO: 2604 Herstatin AF177761.2 CACCCTGTCCTATCCTTCCTCAGACCCTCTTGGGACCTAGTCTCTGCCTTCTACTCTCTACCCC SEQ ID TGGCC NO: 2605 HES6 NM_018645.3 TTAGGGACCCTGCAGCTCTGGAGTGGGTGGAGGGAGGGAGCTACGGGCAGGAGGAAGAATT SEQ ID TTGTAG NO: 2606 HGF M29145.1 CCGAAATCCAGATGATGATGCTCATGGACCCTGGTGCTACACGGGAAATCCACTCATTCCTT SEQ ID GGG NO: 2607 HIF1A NM_001530.1 TGAACATAAAGTCTGCAACATGGAAGGTATTGCACTGCACAGGCCACATTCACGTATATGAT SEQ ID ACCAACAGTAACCAACCTCA NO: 2608 HK1 NM_000188.1 TACGCACAGAGGCAAGCAGCTAAGAGTCCGGGATCCCCAGCCTACTGCCTCTCCAGCACTTC SEQ ID TCTC NO: 2609 HLA-DPB1 NM_002121.4 TCCATGATGGTTCTGCAGGTTTCTGCGGCCCCCCGGACAGTGGCTCTGACGGCGTTACTGAT SEQ ID GGTGCTGCTCA NO: 2610 HLA-DRA NM_019111.3 GACGATTTGCCAGCTTTGAGGCTCAAGGTGCATTGGCCAACATAGCTGTGGACAAAGCCAA SEQ ID CCTGGA NO: 2611 HLA-DRB1 NM_002124.1 GCTTTCTCAGGACCTGGTTGCTACTGGTTCGGCAACTGCAGAAAATGTCCTCCCTTGTGGCTT SEQ ID CCT NO: 2612 HLA-G NM_002127.2 CCTGCGCGGCTACTACAACCAGAGCGAGGCCAGTTCTCACACCCTCCAGTGGATGATTGGCT SEQ ID GCGACCTG NO: 2613 HMGB1 NM_002128.3 TGGCCTGTCCATTGGTGATGTTGCGAAGAAACTGGGAGAGATGTGGAATAACACTGCTGCA SEQ ID GATGACAAGC NO: 2614 hMLH NM_000249.2 CTACTTCCAGCAACCCCAGAAAGAGACATCGGGAAGATTCTGATGTGGAAATGGTGGAAGA SEQ ID TGATTCCCGAAAG NO: 2615 HNRPAB NM_004499.2 CAAGGGAGCGACCAACTGATCGCACACATGCTTTGTTTGGATATGGAGTGAACACAATTATG SEQ ID TACCAAATTTAACTTGGCAAAC NO: 2616 HNRPD NM_031370.2 GCCAGTAAGAACGAGGAGGATGAAGGCCATTCAAACTCCTCCCCACGACACTCTGAAGCAG SEQ ID CGACG NO: 2617 HoxA1 NM_005522.3 AGTGACAGATGGACAATGCAAGAATGAACTCCTTCCTGGAATACCCCATACTTAGCAGTGG SEQ ID CGACTCGG NO: 2618 HoxA5 NM_019102.2 TCCCTTGTGTTCCTTCTGTGAAGAAGCCCTGTTCTCGTTGCCCTAATTCATCTTTTAATCATGA SEQ ID GCCTGTTTATTGCC NO: 2619 HOXB13 NM_006361.2 CGTGCCTTATGGTTACTTTGGAGGCGGGTACTACTCCTGCCGAGTGTCCCGGAGCTCGCTGA SEQ ID AACCCTGTG NO: 2620 HOXB7 NM_004502.2 CAGCCTCAAGTTCGGTTTTCGCTACCGGAGCCTTCCCAGAACAAACTTCTTGTGCGTTTGCTT SEQ ID CCAAC NO: 2621 HRAS NM_005343.2 GGACGAATACGACCCCACTATAGAGGATTCCTACCGGAAGCAGGTGGTCATTGATGGGGAG SEQ ID ACGTGC NO: 2622 HSBP1 NM_001537.1 GGAGATGGCCGAGACTGACCCCAAGACCGTGCAGGACCTCACCTCGGTGGTGCAGACACTC SEQ ID CTGCAG NO: 2623 HSD17B1 NM_000413.1 CTGGACCGCACGGACATCCACACCTTCCACCGCTTCTACCAATACCTCGCCCACAGCAAGCA SEQ ID AGTCTTTCGCGAGGCG NO: 2624 HSD17B2 NM_002153.1 GCTTTCCAAGTGGGGAATTAAAGTTGCTTCCATCCAACCTGGAGGCTTCCTAACAAATATCG SEQ ID CAGGCA NO: 2625 HSPA1A NM_005345.4 CTGCTGCGACAGTCCACTACCTTTTTCGAGAGTGACTCCCGTTGTCCCAAGGCTTCCCAGAG SEQ ID CGAACCTG NO: 2626 HSPA1B NM_005346.3 GGTCCGCTTCGTCTTTCGAGAGTGACTCCCGCGGTCCCAAGGCTTTCCAGAGCGAACCTGTGC SEQ ID NO: 2627 HSPA4 NM_002154.3 TTCAGTGTGTCCAGTGCATCTTTAGTGGAGGTTCACAAGTCTGAGGAAAATGAGGAGCCAAT SEQ ID GGAAACAGAT NO: 2628 HSPA5 NM_005347.2 GGCTAGTAGAACTGGATCCCAACACCAAACTCTTAATTAGACCTAGGCCTCAGCTGCACTGC SEQ ID CCGAAAAGCATTTGGGCAGACC NO: 2629 HSPA8 NM_006597.3 CCTCCCTCTGGTGGTGCTTCCTCAGGGCCCACCATTGAAGAGGTTGATTAAGCCAACCAAGT SEQ ID GTAGATGTAGC NO: 2630 HSPB1 NM_001540.2 CCGACTGGAGGAGCATAAAAGCGCAGCCGAGCCCAGCGCCCCGCACTTTTCTGAGCAGACG SEQ ID TCCAGAGCAGAGTCAGCCAGCAT NO: 2631 HSPCA NM_005348.2 CAAAAGGCAGAGGCTGATAAGAACGACAAGTCTGTGAAGGATCTGGTCATCTTGCTTTATG SEQ ID AAACTGCGCT NO: 2632 HSPE1 NM_002157.1 GCAAGCAACAGTAGTCGCTGTTGGATCGGGTTCTAAAGGAAAGGGTGGAGAGATTCAACCA SEQ ID GTTAGCGTGAAAGTTGG NO: 2633 HSPG2 NM_005529.2 GAGTACGTGTGCCGAGTGTTGGGCAGCTCCGTGCCTCTAGAGGCCTCTGTCCTGGTCACCAT SEQ ID TGAG NO: 2634 ICAM1 NM_000201.1 GCAGACAGTGACCATCTACAGCTTTCCGGCGCCCAACGTGATTCTGACGAAGCCAGAGGTCT SEQ ID CAGAAG NO: 2635 ICAM2 NM_000873.2 GGTCATCCTGACACTGCAACCCACTTTGGTGGCTGTGGGCAAGTCCTTCACCATTGAGTGCA SEQ ID NO: 2636 ID1 NM_002165.1 AGAACCGCAAGGTGAGCAAGGTGGAGATTCTCCAGCACGTCATCGACTACATCAGGGACCT SEQ ID TCAGTTGGA NO: 2637 ID2 NM_002166.1 AACGACTGCTACTCCAAGCTCAAGGAGCTGGTGCCCAGCATCCCCCAGAACAAGAAGGTGA SEQ ID GCAAGATGGAAATCC NO: 2638 ID3 NM_002167.2 CTTCACCAAATCCCTTCCTGGAGACTAAACCTGGTGCTCAGGAGCGAAGGACTGTGAACTTG SEQ ID TAGCCTGAAGAGCCAGAG NO: 2639 ID4 NM_001546.2 TGGCCTGGCTCTTAATTTGCTTTTGTTTTGCCCAGTATAGACTCGGAAGTAAGAGTTATAGCT SEQ ID AGTGGTCTTGCATGATTGCA NO: 2640 IFIT1 NM_001548.1 TGACAACCAAGCAAATGTGAGGAGTCTGGTGACCTGGGGCAACTTTGCCTGGATGTATTACC SEQ ID ACATGGGCAGACTG NO: 2641 IGF1 NM_000618.1 TCCGGAGCTGTGATCTAAGGAGGCTGGAGATGTATTGCGCACCCCTCAAGCCTGCCAAGTCA SEQ ID GCTCGCTCTGTCCG NO: 2642 IGF1R NM_000875.2 GCATGGTAGCCGAAGATTTCACAGTCAAAATCGGAGATTTTGGTATGACGCGAGATATCTAT SEQ ID GAGACAGACTATTACCGGAAA NO: 2643 IGF2 NM_000612.2 CCGTGCTTCCGGACAACTTCCCCAGATACCCCGTGGGCAAGTTCTTCCAATATGACACCTGG SEQ ID AAGCAGTCCA NO: 2644 IGFBP2 NM_000597.1 GTGGACAGCACCATGAACATGTTGGGCGGGGGAGGCAGTGCTGGCCGGAAGCCCCTCAAGT SEQ ID CGGGTATGAAGG NO: 2645 IGFBP3 NM_000598.1 ACGCACCGGGTGTCTGATCCCAAGTTCCACCCCCTCCATTCAAAGATAATCATCATCAAGAA SEQ ID AGGGCA NO: 2646 IGFBP5 NM_000599.1 TGGACAAGTACGGGATGAAGCTGCCAGGCATGGAGTACGTTGACGGGGACTTTCAGTGCCA SEQ ID CACCTTCG NO: 2647 IGFBP6 NM_002178.1 TGAACCGCAGAGACCAACAGAGGAATCCAGGCACCTCTACCACGCCCTCCCAGCCCAATTC SEQ ID TGCGGGTGTCCAAGAC NO: 2648 IGFBP7 NM_001553 GGGTCACTATGGAGTTCAAAGGACAGAACTCCTGCCTGGTGACCGGGACAACCTGGCCATT SEQ ID CAGACCC NO: 2649 IHH NM_002181.1 AAGGACGAGGAGAACACAGGCGCCGACCGCCTCATGACCCAGCGCTGCAAGGACCGCCTGA SEQ ID ACTCGCTGGCTATCT NO: 2650 IL-8 NM_000584.2 AAGGAACCATCTCACTGTGTGTAAACATGACTTCCAAGCTGGCCGTGGCTCTCTTGGCAGCC SEQ ID TTCCTGAT NO: 2651 IL10 NM_000572.1 GGCGCTGTCATCGATTTCTTCCCTGTGAAAACAAGAGCAAGGCCGTGGAGCAGGTGAAGAA SEQ ID TGCCTTTAATAAGCTCCA NO: 2652 IL1B NM_000576.2 AGCTGAGGAAGATGCTGGTTCCCTGCCCACAGACCTTCCAGGAGAATGACCTGAGCACCTTC SEQ ID TTTCC NO: 2653 IL6 NM_000600.1 CCTGAACCTTCCAAAGATGGCTGAAAAAGATGGATGCTTCCAATCTGGATTCAATGAGGAG SEQ ID ACTTGCCTGGT NO: 2654 IL6ST NM_002184.2 GGCCTAATGTTCCAGATCCTTCAAAGAGTCATATTGCCCAGTGGTCACCTCACACTCCTCCA SEQ ID AGGCACAATTTT NO: 2655 ILT-2 NM_006669.1 AGCCATCACTCTCAGTGCAGCCAGGTCCTATCGTGGCCCCTGAGGAGACCCTGACTCTGCAGT SEQ ID NO: 2656 IMP-1 NM_006546.2 GAAAGTGTTTGCGGAGCACAAGATCTCCTACAGCGGCCAGTTCTTGGTCAAATCCGGCTACG SEQ ID CCTTC NO: 2657 IMP2 NM_006548.3 CAATCTGATCCCAGGGTTGAACCTCAGCGCACTTGGCATCTTTTCAACAGGACTGTCCGTGC SEQ ID TATCTCCACCAGCAGGGCC NO: 2658 ING1L NM_001564.1 TGTTTCCAAGATCCTGCTGAAAGTGAACGAGCCTCAGATAAAGCAAAGATGGATTCCAGCC SEQ ID AACCAGAAAGA NO: 2659 ING5 NM_032329.4 CCTACAGCAAGTGCAAGGAATACAGTGACGACAAAGTGCAGCTGGCCATGCAGACCTACGA SEQ ID GATG NO: 2660 INHA NM_002191.2 CCTCCCAGTTTCATCTTCCACTACTGTCATGGTGGTTGTGGGCTGCAGATCCCACCAAACCTG SEQ ID TCCCTTCCAGTCCCT NO: 2661 INHBA NM_002192.1 GTGCCCGAGCCATATAGCAGGCACGTCCGGGTCCTCACTGTCCTTCCACTCAACAGTCATCA SEQ ID ACCACTACCG NO: 2662 INHBB NM_002193.1 AGCCTCCAGGATACCAGCAAATGGATGCGGTGACAAATGGCAGCTTAGCTACAAATGCCTG SEQ ID TCAGTCGGAGA NO: 2663 IRS1 NM_005544.1 CCACAGCTCACCTTCTGTCAGGTGTCCATCCCAGCTCCAGCCAGCTCCCAGAGAGGAAGAGA SEQ ID CTGGCACTGAGG NO: 2664 ITGA3 NM_002204.1 CCATGATCCTCACTCTGCTGGTGGACTATACACTCCAGACCTCGCTTAGCATGGTAAATCAC SEQ ID CGGCTACAAAGCTTC NO: 2665 ITGA4 NM_000885.2 CAACGCTTCAGTGATCAATCCCGGGGCGATTTACAGATGCAGGATCGGAAAGAATCCCGGC SEQ ID CAGAC NO: 2666 ITGA5 NM_002205.1 AGGCCAGCCCTACATTATCAGAGCAAGAGCCGGATAGAGGACAAGGCTCAGATCTTGCTGG SEQ ID ACTGTGGAGAAGAC NO: 2667 ITGA6 NM_000210.1 CAGTGACAAACAGCCCTTCCAACCCAAGGAATCCCACAAAAGATGGCGATGACGCCCATGA SEQ ID GGCTAAAC NO: 2668 ITGA7 NM_002206.1 GATATGATTGGTCGCTGCTTTGTGCTCAGCCAGGACCTGGCCATCCGGGATGAGTTGGATGG SEQ ID TGGGGAATGGAAGTTCT NO: 2669 ITGAV NM_002210.2 ACTCGGACTGCACAAGCTATTTTTGATGACAGCTATTTGGGTTATTCTGTGGCTGTCGGAGAT SEQ ID TTCAATGGTGATGGCA NO: 2670 ITGB1 NM_002211.2 TCAGAATTGGATTTGGCTCATTTGTGGAAAAGACTGTGATGCCTTACATTAGCACAACACCA SEQ ID GCTAAGCTCAGG NO: 2671 ITGB3 NM_000212.1 ACCGGGAGCCCTACATGACCGAAAATACCTGCAACCGTTACTGCCGTGACGAGATTGAGTC SEQ ID AGTGAAAGAGCTTAAGG NO: 2672 ITGB4 NM_000213.2 CAAGGTGCCCTCAGTGGAGCTCACCAACCTGTACCCGTATTGCGACTATGAGATGAAGGTGT SEQ ID GCGC NO: 2673 ITGB5 NM_002213.3 TCGTGAAAGATGACCAGGAGGCTGTGCTATGTTTCTACAAAACCGCCAAGGACTGCGTCATG SEQ ID ATGTTCACC NO: 2674 K-ras NM_033360.2 GTCAAAATGGGGAGGGACTAGGGCAGTTTGGATAGCTCAACAAGATACAATCTCACTCTGT SEQ ID GGTGGTCCTG NO: 2675 KCNH2 iso NM_000238.2 GAGCGCAAAGTGGAAATCGCCTTCTACCGGAAAGATGGGAGCTGCTTCCTATGTCTGGTGG SEQ ID a/b ATGTGGTGCCCGTGAAGA NO: 2676 KCNH2 iso NM_172057.1 TCCTGCTGCTGGTCATCTACACGGCTGTCTTCACACCCTACTCGGCTGCCTTCCTGCTGAAGG SEQ ID a/c AGACGGAAGAAGG NO: 2677 KCNK4 NM_016611.2 CCTATCAGCCGCTGGTGTGGTTCTGGATCCTGCTCGGCCTGGCTTACTTCGCCTCAGTGCTCA SEQ ID CCACCA NO: 2678 KDR NM_002253.1 GAGGACGAAGGCCTCTACACCTGCCAGGCATGCAGTGTTCTTGGCTGTGCAAAAGTGGAGG SEQ ID CATTTTT NO: 2679 Ki-67 NM_002417.1 CGGACTTTGGGTGCGACTTGACGAGCGGTGGTTCGACAAGTGGCCTTGCGGGCCGGATCGTC SEQ ID CCAGTGGAAGAGTTGTAA NO: 2680 KIAA0125 NM_014792.2 GTGTCCTGGTCCATGTGGTGCACGTGTCTCCACCTCCAAGGAGAGGCTCCTCAGTGTGCACC SEQ ID TCCC NO: 2681 KIF22 NM_007317.1 CTAAGGCACTTGCTGGAAGGGCAGAATGCCAGTGTGCTTGCCTATGGACCCACAGGAGCTG SEQ ID GGAAGA NO: 2682 KIF2C NM_006845.2 AATTCCTGCTCCAAAAGAAAGTCTTCGAAGCCGCTCCACTCGCATGTCCACTGTCTCAGAGC SEQ ID TTCGCATCACG NO: 2683 KIFC1 XM_371813.1 CCACAGGGTTGAAGAACCAGAAGCCAGTTCCTGCTGTTCCTGTCCAGAAGTCTGGCACATCA SEQ ID GGTG NO: 2684 Kitlng NM_000899.1 GTCCCCGGGATGGATGTTTTGCCAAGTCATTGTTGGATAAGCGAGATGGTAGTACAATTGTC SEQ ID AGACAGCTTGACTGATC NO: 2685 KLF5 NM_001730.3 GTGCAACCGCAGCTTCTCGCGCTCTGACCACCTGGCCCTGCATATGAAGAGGCACCAGAACT SEQ ID GAGCACTGCCCG NO: 2686 KLF6 NM_001300.4 CACGAGACCGGCTACTTCTCGGCGCTGCCGTCTCTGGAGGAGTACTGGCAACAGACCTGCCT SEQ ID AGAGC NO: 2687 KLK10 NM_002776.1 GCCCAGAGGCTCCATCGTCCATCCTCTTCCTCCCCAGTCGGCTGAACTCTCCCCTTGTCTGCA SEQ ID CTGTTCAAACCTCTG NO: 2688 KLK6 NM_002774.2 GACGTGAGGGTCCTGATTCTCCCTGGTTTTACCCCAGCTCCATCCTTGCATCACTGGGGAGG SEQ ID ACGTGATGAGTGAGGA NO: 2689 KLRK1 NM_007360.1 TGAGAGCCAGGCTTCTTGTATGTCTCAAAATGCCAGCCTTCTGAAAGTATACAGCAAAGAGG SEQ ID ACCAGGAT NO: 2690 KNTC2 NM_006101.1 ATGTGCCAGTGAGCTTGAGTCCTTGGAGAAACACAAGCACCTGCTAGAAAGTACTGTTAACC SEQ ID AGGGGCTCA NO: 2691 KRAS2 NM_004985.3 GAGACCAAGGTTGCAAGGCCAGGCCCTGTGTGAACCTTTGAGCTTTCATAGAGAGTTTCACA SEQ ID GCATGGACTG NO: 2692 KRT19 NM_002276.1 TGAGCGGCAGAATCAGGAGTACCAGCGGCTCATGGACATCAAGTCGCGGCTGGAGCAGGAG SEQ ID ATTGCCACCTACCGCA NO: 2693 KRT8 NM_002273.1 GGATGAAGCTTACATGAACAAGGTAGAGCTGGAGTCTCGCCTGGAAGGGCTGACCGACGAG SEQ ID ATCAACTTCCTCAGGCAGCTATATG NO: 2694 LAMA3 NM_000227.2 CAGATGAGGCACATGGAGACCCAGGCCAAGGACCTGAGGAATCAGTTGCTCAACTACCGTT SEQ ID CTGCCATTTCAA NO: 2695 LAMB3 NM_000228.1 ACTGACCAAGCCTGAGACCTACTGCACCCAGTATGGCGAGTGGCAGATGAAATGCTGCAAG SEQ ID TGTGAC NO: 2696 LAMC2 NM_005562.1 ACTCAAGCGGAAATTGAAGCAGATAGGTCTTATCAGCACAGTCTCCGCCTCCTGGATTCAGT SEQ ID GTCTCGGCTTCAGGGAGT NO: 2697 LAT NM_014387.2 GTGAACGTTCCGGAGAGCGGGGAGAGCGCAGAAGCGTCTCTGGATGGCAGCCGGGAGTATG SEQ ID TGAATGT NO: 2698 LCN2 NM_005564.2 CGCTGGGCAACATTAAGAGTTACCCTGGATTAACGAGTTACCTCGTCCGAGTGGTGAGCACC SEQ ID AACTACAACCAGCATGCT NO: 2699 LDLRAP1 NM_015627.1 CAGTGCCTCTCGCCTGTCGACTGGGACAAGCCTGACAGCAGCGGCACAGAGCAGGATGACC SEQ ID TCTTCA NO: 2700 LEF NM_016269.2 GATGACGGAAAGCATCCAGATGGAGGCCTCTACAACAAGGGACCCTCCTACTCGAGTTATT SEQ ID CCGGG NO: 2701 LGALS3 NM_002306.1 AGCGGAAAATGGCAGACAATTTTTCGCTCCATGATGCGTTATCTGGGTCTGGAAACCCAAAC SEQ ID CCTCAAG NO: 2702 LGMN NM_001008530.1 TTGGTGCCGTTCCTATAGATGATCCTGAAGATGGAGGCAAGCACTGGGTGGTGATCGTGGCA SEQ ID GGTTC NO: 2703 LILRB3 NM_006864.1 CACCTGGTCTGGGAAGATACCTGGAGGTTTTGATTGGGGTCTCGGTGGCCTTCGTCCTGCTG SEQ ID CTCTT NO: 2704 LMNB1 NM_005573.1 TGCAAACGCTGGTGTCACAGCCAGCCCCCCAACTGACCTCATCTGGAAGAACCAGAACTCGT SEQ ID GGGG NO: 2705 LMYC NM_012421.1 CCCATCCAGAACACTGATTGCTGTCATTCAAGTGAAAGGGATGGAGGTCAGAAAGGGTGCA SEQ ID TAGAAAGCAG NO: 2706 LOX NM_002317.3 CCAATGGGAGAACAACGGGCAGGTGTTCAGCTTGCTGAGCCTGGGCTCACAGTACCAGCCT SEQ ID CAGCG NO: 2707 LOXL2 NM_002318.1 TCAGCGGGCTCTTAAACAACCAGCTGTCCCCGCAGTAAAGAAGCCTGCGTGGTCAACTCCTG SEQ ID TCTT NO: 2708 LRP5 NM_002335.1 CGACTATGACCCACTGGACAAGTTCATCTACTGGGTGGATGGGCGCCAGAACATCAAGCGA SEQ ID GCCAAG NO: 2709 LRP6 NM_002336.1 GGATGTAGCCATCTCTGCCTCTATAGACCTCAGGGCCTTCGCTGTGCTTGCCCTATTGGCTTT SEQ ID GAACT NO: 2710 LY6D NM_003695.2 AATGCTGATGACTTGGAGCAGGCCCCACAGACCCCACAGAGGATGAAGCCACCCCACAGAG SEQ ID GATGCAG NO: 2711 MAD NM_002357.1 TGGTTCTGATTAGGTAACGTATTGGACCTGCCCACAACTCCCTTGCACGTAAACTTCAGTGTC SEQ ID CCACCTTGACC NO: 2712 MAD1L1 NM_003550.1 AGAAGCTGTCCCTGCAAGAGCAGGATGCAGCGATTGTGAAGAACATGAAGTCTGAGCTGGT SEQ ID ACGGCT NO: 2713 MAD2L1 NM_002358.2 CCGGGAGCAGGGAATCACCCTGCGCGGGAGCGCCGAAATCGTGGCCGAGTTCTTCTCATTC SEQ ID GGCATCAACAGCAT NO: 2714 MADH2 NM_005901.2 GCTGCCTTTGGTAAGAACATGTCGTCCATCTTGCCATTCACGCCGCCAGTTGTGAAGAGACT SEQ ID GCTGGGAT NO: 2715 MADH4 NM_005359.3 GGACATTACTGGCCTGTTCACAATGAGCTTGCATTCCAGCCTCCCATTTCCAATCATCCTGCT SEQ ID CCTGAGTATTGGT NO: 2716 MADH7 NM_005904.1 TCCATCAAGGCTTTCGACTACGAGAAGGCGTACAGCCTGCAGCGGCCCAATGACCACGAGT SEQ ID TTATGCAGCAG NO: 2717 MAP2 NM_031846.1 CGGACCACCAGGTCAGAGCCAATTCGCAGAGCAGGGAAGAGTGGTACCTCAACACCCACTA SEQ ID CCCCTG NO: 2718 MAP2K1 NM_002755.2 GCCTTTCTTACCCAGAAGCAGAAGGTGGGAGAACTGAAGGATGACGACTTTGAGAAGATCA SEQ ID GTGAGCTGGGGGCTG NO: 2719 MAP3K1 XM_042066.8 GGTTGGCATCAAAAGGAACTGGTGCAGGAGAGTTTCAGGGACAATTACTGGGGACAATTGC SEQ ID ATTTATGGCA NO: 2720 MAPK14 NM_139012.1 TGAGTGGAAAAGCCTGACCTATGATGAAGTCATCAGCTTTGTGCCACCACCCCTTGACCAAG SEQ ID AAGAGATGGAGTCC NO: 2721 Maspin NM_002639.1 CAGATGGCCACTTTGAGAACATTTTAGCTGACAACAGTGTGAACGACCAGACCAAAATCCTT SEQ ID GTGGTTAATGCTGCC NO: 2722 MAX NM_002382.3 CAAACGGGCTCATCATAATGCACTGGAACGAAAACGTAGGGACCACATCAAAGACAGCTTT SEQ ID CACAGTTTGCGGGA NO: 2723 MCM2 NM_004526.1 GACTTTTGCCCGCTACCTTTCATTCCGGCGTGACAACAATGAGCTGTTGCTCTTCATACTGAA SEQ ID GCAGTTAGTGGC NO: 2724 MCM3 NM_002388.2 GGAGAACAATCCCCTTGAGACAGAATATGGCCTTTCTGTCTACAAGGATCACCAGACCATCA SEQ ID CCATCCAGGAGAT NO: 2725 MCM6 NM_005915.2 TGATGGTCCTATGTGTCACATTCATCACAGGTTTCATACCAACACAGGCTTCAGCACTTCCTT SEQ ID TGGTGTGTTTCCTGTCCCA NO: 2726 MCP1 NM_002982.1 CGCTCAGCCAGATGCAATCAATGCCCCAGTCACCTGCTGTTATAACTTCACCAATAGGAAGA SEQ ID TCTCAGTGC NO: 2727 MDK NM_002391.2 GGAGCCGACTGCAAGTACAAGTTTGAGAACTGGGGTGCGTGTGATGGGGGCACAGGCACCA SEQ ID AAGTC NO: 2728 MDM2 NM_002392.1 CTACAGGGACGCCATCGAATCCGGATCTTGATGCTGGTGTAAGTGAACATTCAGGTGATTGG SEQ ID TTGGAT NO: 2729 MGAT5 NM_002410.2 GGAGTCGAAGGTGGACAATCTTGTTGTCAATGGCACCGGAACAAACTCAACCAACTCCACT SEQ ID ACAGCTGTTCCCA NO: 2730 MGMT NM_002412.1 GTGAAATGAAACGCACCACACTGGACAGCCCTTTGGGGAAGCTGGAGCTGTCTGGTTGTGA SEQ ID GCAGGGTC NO: 2731 mGST1 NM_020300.2 ACGGATCTACCACACCATTGCATATTTGACACCCCTTCCCCAGCCAAATAGAGCTTTGAGTT SEQ ID TTTTTGTTGGATATGGA NO: 2732 MMP1 NM_002421.2 GGGAGATCATCGGGACAACTCTCCTTTTGATGGACCTGGAGGAAATCTTGCTCATGCTTTTC SEQ ID AACCAGGCCC NO: 2733 MMP12 NM_002426.1 CCAACGCTTGCCAAATCCTGACAATTCAGAACCAGCTCTCTGTGACCCCAATTTGAGTTTTG SEQ ID ATGCTGTCACTACCGT NO: 2734 MMP2 NM_004530.1 CCATGATGGAGAGGCAGACATCATGATCAACTTTGGCCGCTGGGAGCATGGCGATGGATAC SEQ ID CCCTTTGACGGTAAGGACGGACTCC NO: 2735 MMP7 NM_002423.2 GGATGGTAGCAGTCTAGGGATTAACTTCCTGTATGCTGCAACTCATGAACTTGGCCATTCTTT SEQ ID GGGTATGGGACATTCC NO: 2736 MMP9 NM_004994.1 GAGAACCAATCTCACCGACAGGCAGCTGGCAGAGGAATACCTGTACCGCTATGGTTACACT SEQ ID CGGGTG NO: 2737 MRP1 NM_004996.2 TCATGGTGCCCGTCAATGCTGTGATGGCGATGAAGACCAAGACGTATCAGGTGGCCCACAT SEQ ID GAAGAGCAAAGACAATCG NO: 2738 MRP2 NM_000392.1 AGGGGATGACTTGGACACATCTGCCATTCGACATGACTGCAATTTTGACAAAGCCATGCAGT SEQ ID TTT NO: 2739 MRP3 NM_003786.2 TCATCCTGGCGATCTACTTCCTCTGGCAGAACCTAGGTCCCTCTGTCCTGGCTGGAGTCGCTT SEQ ID TCATGGTCTTGCTGATTCCACTCAACGG NO: 2740 MRP4 NM_005845.1 AGCGCCTGGAATCTACAACTCGGAGTCCAGTGTTTTCCCACTTGTCATCTTCTCTCCAGGGGC SEQ ID TCT NO: 2741 MRPL40 NM_003776.2 ACTTGCAGGCTGCTATCCTTAACATGCTGCCCCTGAGAGTAGGAATGACCAGGGTTCAAGTC SEQ ID TGCT NO: 2742 MSH2 NM_000251.1 GATGCAGAATTGAGGCAGACTTTACAAGAAGATTTACTTCGTCGATTCCCAGATCTTAACCG SEQ ID ACTTGCCAAGA NO: 2743 MSH3 NM_002439.1 TGATTACCATCATGGCTCAGATTGGCTCCTATGTTCCTGCAGAAGAAGCGACAATTGGGATT SEQ ID GTGGATGGCATTTTCACAAG NO: 2744 MSH6 NM_000179.1 TCTATTGGGGGATTGGTAGGAACCGTTACCAGCTGGAAATTCCTGAGAATTTCACCACTCGC SEQ ID AATTTG NO: 2745 MT3 NM_005954.1 GTGTGAGAAGTGTGCCAAGGACTGTGTGTGCAAAGGCGGAGAGGCAGCTGAGGCAGAAGC SEQ ID AGAGAAGTGCAG NO: 2746 MTA1 NM_004689.2 CCGCCCTCACCTGAAGAGAAACGCGCTCCTTGGCGGACACTGGGGGAGGAGAGGAAGAAGC SEQ ID GCGGCTAACTTATTCC NO: 2747 MUC1 NM_002456.1 GGCCAGGATCTGTGGTGGTACAATTGACTCTGGCCTTCCGAGAAGGTACCATCAATGTCCAC SEQ ID GACGTGGAG NO: 2748 MUC2 NM_002457.1 CTATGAGCCATGTGGGAACCGGAGCTTCGAGACCTGCAGGACCATCAACGGCATCCACTCC SEQ ID AACAT NO: 2749 MUC5B XM_039877.11 TGCCCTTGCACTGTCCTAACGGCTCAGCCATCCTGCACACCTACACCCACGTGGATGAGTGT SEQ ID GGCTG NO: 2750 MUTYH NM_012222.1 GTACGACCAAGAGAAACGGGACCTACCATGGAGAAGACGGGCAGAAGATGAGATGGACCT SEQ ID GGACAGG NO: 2751 MVP NM_017458.1 ACGAGAACGAGGGCATCTATGTGCAGGATGTCAAGACCGGAAAGGTGCGCGCTGTGATTGG SEQ ID AAGCACCTACATGC NO: 2752 MX1 NM_002462.2 GAAGGAATGGGAATCAGTCATGAGCTAATCACCCTGGAGATCAGCTCCCGAGATGTCCCGG SEQ ID ATCTGACTCTAATAGAC NO: 2753 MXD4 NM_006454.2 AGAAACTGGAGGAGCAGGACCGCCGGGCACTGAGCATCAAGGAGCAGCTGCAGCAGGAGC SEQ ID ATCGTTTCCTGAAG NO: 2754 MYBL2 NM_002466.1 GCCGAGATCGCCAAGATGTTGCCAGGGAGGACAGACAATGCTGTGAAGAATCACTGGAACT SEQ ID CTACCATCAAAAG NO: 2755 MYH11 NM_002474.1 CGGTACTTCTCAGGGCTAATATATACGTACTCTGGCCTCTTCTGCGTGGTGGTCAACCCCTAT SEQ ID AAACACCTGCCCATCTACTCGG NO: 2756 MYLK NM_053025.1 TGACGGAGCGTGAGTGCATCAAGTACATGCGGCAGATCTCGGAGGGAGTGGAGTACATCCA SEQ ID CAAGCAGGGCAT NO: 2757 NAT2 NM_000015.1 TAACTGACATTCTTGAGCACCAGATCCGGGCTGTTCCCTTTGAGAACCTTAACATGCATTGT SEQ ID GGGCAAGCCAT NO: 2758 NAV2 NM_182964.3 CTCTCCCAGCACAGCTTGAACCTCACTGAGTCAACCAGCCTGGACATGTTGCTGGATGACAC SEQ ID TGGTG NO: 2759 NCAM1 NM_000615.1 TAGTTCCCAGCTGACCATCAAAAAGGTGGATAAGAACGACGAGGCTGAGTACATCTGCATT SEQ ID GCTGAGAACAAGGCTG NO: 2760 NDE1 NM_017668.1 CTACTGCGGAAAGTCGGGGCACTGGAGTCCAAACTCGCTTCCTGCCGGAACCTCGTGTACGA SEQ ID TCAGTCC NO: 2761 NDRG1 NM_006096.2 AGGGCAACATTCCACAGCTGCCCTGGCTGTGATGAGTGTCCTTGCAGGGGCCGGAGTAGGA SEQ ID GCACTG NO: 2762 NDUFS3 NM_004551.1 TATCCATCCTGATGGCGTCATCCCAGTGCTGACTTTCCTCAGGGATCACACCAATGCACAGT SEQ ID TCAA NO: 2763 NEDD8 NM_006156.1 TGCTGGCTACTGGGTGTTAGTTTGCAGTCCTGTGTGCTTCCCTCTCTTATGACTGTGTCCCTG SEQ ID GTTGTC NO: 2764 NEK2 NM_002497.1 GTGAGGCAGCGCGACTCTGGCGACTGGCCGGCCATGCCTTCCCGGGCTGAGGACTATGAAG SEQ ID TGTTGTACACCATTGGCA NO: 2765 NF2 NM_000268.2 ACTCCAGAGCTGACCTCCACCGCCCAGCCTGGGAAGTCATTGTAGGGAGTGAGACACTGAA SEQ ID GCCCTGA NO: 2766 NFKBp50 NM_003998.1 CAGACCAAGGAGATGGACCTCAGCGTGGTGCGGCTCATGTTTACAGCTTTTCTTCCGGATAG SEQ ID CACTGGCAGCT NO: 2767 NFKBp65 NM_021975.1 CTGCCGGGATGGCTTCTATGAGGCTGAGCTCTGCCCGGACCGCTGCATCCACAGTTTCCAGA SEQ ID ACCTGG NO: 2768 NISCH NM_007184.1 CCAAGGAATCATGTTCGTTCAGGAGGAGGCCCTGGCCAGCAGCCTCTCGTCCACTGACAGTC SEQ ID TGACTCCCGAGCACCA NO: 2769 Nkd-1 NM_033119.3 GAGAGAGTGAGCGAACCCTGCCCAGGCTCCAAGAAGCAGCTGAAGTTTGAAGAGCTCCAGT SEQ ID GCGACG NO: 2770 NMB NM_021077.1 GGCTGCTGGTACAAATACTGCAGAAATGACACCAATAATAGGGGCAGACACAACAGCGTGG SEQ ID CTTAGATTG NO: 2771 NMBR NM_002511.1 TGATCCATCTCTAGGCCACATGATTGTCACCTTAGTTGCCCGGGTTCTCAGTTTTGGCAATTC SEQ ID TTGTGTCAACCCATTTGCTC NO: 2772 NME1 NM_000269.1 CCAACCCTGCAGACTCCAAGCCTGGGACCATCCGTGGAGACTTCTGCATACAAGTTGGCAGG SEQ ID AACATTATACAT NO: 2773 NOS3 NM_000603.2 ATCTCCGCCTCGCTCATGGGCACGGTGATGGCGAAGCGAGTGAAGGCGACAATCCTGTATG SEQ ID GCTCCGA NO: 2774 NOTCH1 NM_017617.2 CGGGTCCACCAGTTTGAATGGTCAATGCGAGTGGCTGTCCCGGCTGCAGAGCGGCATGGTGC SEQ ID CGAACCAATACAAC NO: 2775 NOTCH2 NM_024408.2 CACTTCCCTGCTGGGATTATATCAACAACCAGTGTGATGAGCTGTGCAACACGGTCGAGTGC SEQ ID CTGTTTGACAACT NO: 2776 NPM1 NM_002520.2 AATGTTGTCCAGGTTCTATTGCCAAGAATGTGTTGTCCAAAATGCCTGTTTAGTTTTTAAAGA SEQ ID TGGAACTCCACCCTTTGCTTG NO: 2777 NR4A1 NM_002135.2 CACAGCTTGCTTGTCGATGTCCCTGCCTTCGCCTGCCTCTCTGCCCTTGTCCTCATCACCGAC SEQ ID CGGCAT NO: 2778 NRG1 NM_013957.1 CGAGACTCTCCTCATAGTGAAAGGTATGTGTCAGCCATGACCACCCCGGCTCGTATGTCACC SEQ ID TGTAGATTTCCACACGCCAAG NO: 2779 NRP1 NM_003873.1 CAGCTCTCTCCACGCGATTCATCAGGATCTACCCCGAGAGAGCCACTCATGGCGGACTGGGG SEQ ID CTCAGAATGGAGCTGCTGGG NO: 2780 NRP2 NM_003872.1 CTACAGCCTAAACGGCAAGGACTGGGAATACATTCAGGACCCCAGGACCCAGCAGCCAAAG SEQ ID CTGTTCGAAGGGAAC NO: 2781 NTN1 NM_004822.1 AGAAGGACTATGCCGTCCAGATCCACATCCTGAAGGCGGACAAGGCGGGGGACTGGTGGAA SEQ ID GTTCACGG NO: 2782 NUFIP1 NM_012345.1 GCTTCCACATCGTGGTATTGGAGACAGTCTTCTGATAGGTTTCCTCGGCATCAGAAGTCCTTC SEQ ID AACCCTGCAGTT NO: 2783 ODC1 NM_002539.1 AGAGATCACCGGCGTAATCAACCCAGCGTTGGACAAATACTTTCCGTCAGACTCTGGAGTGA SEQ ID GAATCATAGCTGAGCCCG NO: 2784 OPN, NM_000582.1 CAACCGAAGTTTTCACTCCAGTTGTCCCCACAGTAGACACATATGATGGCCGAGGTGATAGT SEQ ID osteopontin GTGGTTTATGGACTGAGG NO: 2785 ORC1L NM_004153.2 TCCTTGACCATACCGGAGGGTGCATGTACATCTCCGGTGTCCCTGGGACAGGGAAGACTGCC SEQ ID ACTG NO: 2786 OSM NM_020530.3 GTTTCTGAAGGGGAGGTCACAGCCTGAGCTGGCCTCCTATGCCTCATCATGTCCCAAACCAG SEQ ID ACACCT NO: 2787 OSMR NM_003999.1 GCTCATCATGGTCATGTGCTACTTGAAAAGTCAGTGGATCAAGGAGACCTGTTATCCTGACA SEQ ID TCCCTGACCCTTACA NO: 2788 P14ARF S78535.1 CCCTCGTGCTGATGCTACTGAGGAGCCAGCGTCTAGGGCAGCAGCCGCTTCCTAGAAGACCA SEQ ID GGTCATGATG NO: 2789 p16-INK4 L27211.1 GCGGAAGGTCCCTCAGACATCCCCGATTGAAAGAACCAGAGAGGCTCTGAGAAACCTCGGG SEQ ID AAACTTAGATCATCA NO: 2790 p21 NM_000389.1 TGGAGACTCTCAGGGTCGAAAACGGCGGCAGACCAGCATGACAGATTTCTACCACTCCAAA SEQ ID CGCC NO: 2791 p27 NM_004064.1 CGGTGGACCACGAAGAGTTAACCCGGGACTTGGAGAAGCACTGCAGAGACATGGAAGAGG SEQ ID CGAGCC NO: 2792 P53 NM_000546.2 CTTTGAACCCTTGCTTGCAATAGGTGTGCGTCAGAAGCACCCAGGACTTCCATTTGCTTTGTC SEQ ID CCGGG NO: 2793 p53R2 AB036063.1 CCCAGCTAGTGTTCCTCAGAACAAAGATTGGAAAAAGCTGGCCGAGAACCATTTATACATA SEQ ID GAGGAAGGGCTTACGG NO: 2794 PADI4 NM_012387.1 AGCAGTGGCTTGCTTTCTTCTCCTGTGATGTCCCAGTTTCCCACTCTGAAGATCCCAACATGG SEQ ID TCCTAGCA NO: 2795 PAI1 NM_000602.1 CCGCAACGTGGTTTTCTCACCCTATGGGGTGGCCTCGGTGTTGGCCATGCTCCAGCTGACAA SEQ ID CAGGAGGAGAAACCCAGCA NO: 2796 Pak1 NM_002576.3 GAGCTGTGGGTTGTTATGGAATACTTGGCTGGAGGCTCCTTGACAGATGTGGTGACAGAAAC SEQ ID TTGCATGG NO: 2797 PARC NM_015089.1 GGAGCTGACCTGCTTCCTACATCGCCTGGCCTCGATGCATAAGGACTATGCTGTGGTGCTCT SEQ ID GCT NO: 2798 PCAF NM_003884.3 AGGTGGCTGTGTTACTGCAACGTGCCACAGTTCTGCGACAGTCTACCTCGGTACGAAACCAC SEQ ID ACAGGTG NO: 2799 PCNA NM_002592.1 GAAGGTGTTGGAGGCACTCAAGGACCTCATCAACGAGGCCTGCTGGGATATTAGCTCCAGC SEQ ID GGTGTAAACC NO: 2800 PDGFA NM_002607.2 TTGTTGGTGTGCCCTGGTGCCGTGGTGGCGGTCACTCCCTCTGCTGCCAGTGTTTGGACAGA SEQ ID ACCCA NO: 2801 PDGFB NM_002608.1 ACTGAAGGAGACCCTTGGAGCCTAGGGGCATCGGCAGGAGAGTGTGTGGGCAGGGTTATTTA SEQ ID NO: 2802 PDGFC NM_016205.1 AGTTACTAAAAAATACCACGAGGTCCTTCAGTTGAGACCAAAGACCGGTGTCAGGGGATTG SEQ ID CACAAATCACTCACCGAC NO: 2803 PDGFD NM_025208.2 TATCGAGGCAGGTCATACCATGACCGGAAGTCAAAAGTTGACCTGGATAGGCTCAATGATG SEQ ID ATGCCAAGCGTTA NO: 2804 PDGFRa NM_006206.2 GGGAGTTTCCAAGAGATGGACTAGTGCTTGGTCGGGTCTTGGGGTCTGGAGCGTTTGGGAAG SEQ ID GTGGTTGAAG NO: 2805 PDGFRb NM_002609.2 CCAGCTCTCCTTCCAGCTACAGATCAATGTCCCTGTCCGAGTGCTGGAGCTAAGTGAGAGCC SEQ ID ACCC NO: 2806 PFN1 NM_005022.2 GGAAAACGTTCGTCAACATCACGCCAGCTGAGGTGGGTGTCCTGGTTGGCAAAGACCGGTC SEQ ID AAGTTTT NO: 2807 PFN2 NM_053024.1 TCTATACGTCGATGGTGACTGCACAATGGACATCCGGACAAAGAGTCAAGGTGGGGAGCCA SEQ ID ACATACAATGTGGCTGTCGGC NO: 2808 PGK1 NM_000291.1 AGAGCCAGTTGCTGTAGAACTCAAATCTCTGCTGGGCAAGGATGTTCTGTTCTTGAAGGACT SEQ ID GTGTAGGCCCAG NO: 2809 PI3K NM_002646.2 TGCTACCTGGACAGCCCGTTGGTGCGCTTCCTCCTGAAACGAGCTGTGTCTGACTTGAGAGT SEQ ID GACTCACTACTTCTTCTGGTTACTGAAGGACGGCCT NO: 2810 PI3KC2A NM_002645.1 ATACCAATCACCGCACAAACCCAGGCTATTTGTTAAGTCCAGTCACAGCGCAAAGAAACAT SEQ ID ATGCGGAGAAAATGCTAGTGTG NO: 2811 PIK3CA NM_006218.1 GTGATTGAAGAGCATGCCAATTGGTCTGTATCCCGAGAAGCAGGATTTAGCTATTCCCACGC SEQ ID AGGAC NO: 2812 PIM1 NM_002648.2 CTGCTCAAGGACACCGTCTACACGGACTTCGATGGGACCCGAGTGTATAGCCCTCCAGAGTG SEQ ID GATCC NO: 2813 Pin1 NM_006221.1 GATCAACGGCTACATCCAGAAGATCAAGTCGGGAGAGGAGGACTTTGAGTCTCTGGCCTCA SEQ ID CAGTTCA NO: 2814 PKD1 NM_000296.2 CAGCACCAGCGATTACGACGTTGGCTGGGAGAGTCCTCACAATGGCTCGGGGACGTGGGCC SEQ ID TATTCAG NO: 2815 PKR2 NM_002654.3 CCGCCTGGACATTGATTCACCACCCATCACAGCCCGGAACACTGGCATCATCTGTACCATTG SEQ ID GCCCAG NO: 2816 PLA2G2A NM_000300.2 GCATCCCTCACCCATCCTAGAGGCCAGGCAGGAGCCCTTCTATACCCACCCAGAATGAGACA SEQ ID TCCAGCAGATTTCCAGC NO: 2817 PLAUR NM_002659.1 CCCATGGATGCTCCTCTGAAGAGACTTTCCTCATTGACTGCCGAGGCCCCATGAATCAATGT SEQ ID CTGGTAGCCACCGG NO: 2818 PLK NM_005030.2 AATGAATACAGTATTCCCAAGCACATCAACCCCGTGGCCGCCTCCCTCATCCAGAAGATGCT SEQ ID TCAGACA NO: 2819 PLK3 NM_004073.2 TGAAGGAGACGTACCGCTGCATCAAGCAGGTTCACTACACGCTGCCTGCCAGCCTCTCACTG SEQ ID CCTG NO: 2820 PLOD2 NM_000935.2 CAGGGAGGTGGTTGCAAATTTCTAAGGTACAATTGCTCTATTGAGTCACCACGAAAAGGCTG SEQ ID GAGCTTCATGCATCCTGGGAGA NO: 2821 PMS1 NM_000534.2 CTTACGGTTTTCGTGGAGAAGCCTTGGGGTCAATTTGTTGTATAGCTGAGGTTTTAATTACAA SEQ ID CAAGAACGGCTGCT NO: 2822 PMS2 NM_000535.2 GATGTGGACTGCCATTCAAACCAGGAAGATACCGGATGTAAATTTCGAGTTTTGCCTCAGCC SEQ ID AACTAATCTCGCA NO: 2823 PPARG NM_005037.3 TGACTTTATGGAGCCCAAGTTTGAGTTTGCTGTGAAGTTCAATGCACTGGAATTAGATGACA SEQ ID GCGACTTGGC NO: 2824 PPID NM_005038.1 TCCTCATTTGGATGGGAAACATGTGGTGTTTGGCCAAGTAATTAAAGGAATAGGAGTGGCA SEQ ID AGGATATTGG NO: 2825 PPM1D NM_003620.1 GCCATCCGCAAAGGCTTTCTCGCTTGTCACCTTGCCATGTGGAAGAAACTGGCGGAATGGCC SEQ ID NO: 2826 PPP2R4 NM_178001.1 GGCTCAGAGCATAAGGCTTCAGGGCCCAAGTTGGGAGAAGTGACCAAAGTGTAGCCAGTTT SEQ ID TCTGAGTTCCCGT NO: 2827 PR NM_000926.2 GCATCAGGCTGTCATTATGGTGTCCTTACCTGTGGGAGCTGTAAGGTCTTCTTTAAGAGGGC SEQ ID AATGGAAGGGCAGCACAACTACT NO: 2828 PRDX2 NM_005809.4 GGTGTCCTTCGCCAGATCACTGTTAATGATTTGCCTGTGGGACGCTCCGTGGATGAGGCTCT SEQ ID GCGGCTG NO: 2829 PRDX3 NM_006793.2 TGACCCCAATGGAGTCATCAAGCATTTGAGCGTCAACGATCTCCCAGTGGGCCGAAGCGTG SEQ ID GAAGAAACCCTCCGCTTGG NO: 2830 PRDX4 NM_006406.1 TTACCCATTTGGCCTGGATTAATACCCCTCGAAGACAAGGAGGACTTGGGCCAATAAGGATT SEQ ID CCACTTCTTTCAG NO: 2831 PRDX6 NM_004905.2 CTGTGAGCCAGAGGATGTCAGCTGCCAATTGTGTTTTCCTGCAGCAATTCCATAAACACATC SEQ ID CTGGTGTCATCACA NO: 2832 PRKCA NM_002737.1 CAAGCAATGCGTCATCAATGTCCCCAGCCTCTGCGGAATGGATCACACTGAGAAGAGGGGG SEQ ID CGGATTTAC NO: 2833 PRKCB1 NM_002738.5 GACCCAGCTCCACTCCTGCTTCCAGACCATGGACCGCCTGTACTTTGTGATGGAGTACGTGA SEQ ID ATGGG NO: 2834 PRKCD NM_006254.1 CTGACACTTGCCGCAGAGAATCCCTTTCTCACCCACCTCATCTGCACCTTCCAGACCAAGGA SEQ ID CCACCT NO: 2835 PRKR NM_002759.1 GCGATACATGAGCCCAGAACAGATTTCTTCGCAAGACTATGGAAAGGAAGTGGACCTCTAC SEQ ID GCTTTGGGGCTAATTCTTGCTGA NO: 2836 pS2 NM_003225.1 GCCCTCCCAGTGTGCAAATAAGGGCTGCTGTTTCGACGACACCGTTCGTGGGGTCCCCTGGT SEQ ID GCTTCTATCCTAATACCATCGACG NO: 2837 PTCH NM_000264.2 CCACGACAAAGCCGACTACATGCCTGAAACAAGGCTGAGAATCCCGGCAGCAGAGCCCATC SEQ ID GAGTA NO: 2838 PTEN NM_000314.1 TGGCTAAGTGAAGATGACAATCATGTTGCAGCAATTCACTGTAAAGCTGGAAAGGGACGAA SEQ ID CTGGTGTAATGATATGTGCA NO: 2839 PTGER3 NM_000957.2 TAACTGGGGCAACCTTTTCTTCGCCTCTGCCTTTGCCTTCCTGGGGCTCTTGGCGCTGACAGT SEQ ID CACCTTTTCCTGCAA NO: 2840 PTHLH NM_002820.1 AGTGACTGGGAGTGGGCTAGAAGGGGACCACCTGTCTGACACCTCCACAACGTCGCTGGAG SEQ ID CTCGATTCACGGTAACAGGCTT NO: 2841 PTHR1 NM_000316.1 CGAGGTACAAGCTGAGATCAAGAAATCTTGGAGCCGCTGGACACTGGCACTGGACTTCAAG SEQ ID CGAAAGGCACGC NO: 2842 PTK2 NM_005607.3 GACCGGTCGAATGATAAGGTGTACGAGAATGTGACGGGCCTGGTGAAAGCTGTCATCGAGA SEQ ID TGTCCAG NO: 2843 PTK2B NM_004103.3 CAAGCCCAGCCGACCTAAGTACAGACCCCCTCCGCAAACCAACCTCCTGGCTCCAAAGCTG SEQ ID CAGTTCCAGGTTC NO: 2844 PTP4A3 NM_007079.2 AATATTTGTGCGGGGTATGGGGGTGGGTTTTTAAATCTCGTTTCTCTTGGACAAGCACAGGG SEQ ID ATCTCGTT NO: 2845 PTP4A3 v2 NM_032611.1 CCTGTTCTCGGCACCTTAAATTATTAGACCCCGGGGCAGTCAGGTGCTCCGGACACCCGAAG SEQ ID GCAATA NO: 2846 PTPD1 NM_007039.2 CGCTTGCCTAACTCATACTTTCCCGTTGACACTTGATCCACGCAGCGTGGCACTGGGACGTA SEQ ID AGTGGCGCAGTCTGAATGG NO: 2847 PTPN1 NM_002827.2 AATGAGGAAGTTTCGGATGGGGCTGATCCAGACAGCCGACCAGCTGCGCTTCTCCTACCTGG SEQ ID CTGTGATCGAAG NO: 2848 PTPRF NM_002840.2 TGTTTTAGCTGAGGGACGTGGTGCCGACGTCCCCAAACCTAGCTAGGCTAAGTCAAGATCAA SEQ ID CATTCCAGGGTTGGTA NO: 2849 PTPRJ NM_002843.2 AACTTCCGGTACCTCGTTCGTGACTACATGAAGCAGAGTCCTCCCGAATCGCCGATTCTGGT SEQ ID GCATTGCAGTGCT NO: 2850 PTPRO NM_030667.1 CATGGCCTGATCATGGTGTGCCCACAGCAAATGCTGCAGAAAGTATCCTGCAGTTTGTACAC SEQ ID ATGG NO: 2851 PTTG1 NM_004219.2 GGCTACTCTGATCTATGTTGATAAGGAAAATGGAGAACCAGGCACCCGTGTGGTTGCTAAG SEQ ID GATGGGCTGAAGC NO: 2852 RAB32 NM_006834.2 CCTGCAGCTGTGGGACATCGCGGGGCAGGAGCGATTTGGCAACATGACCCGAGTATACTAC SEQ ID AAGGAAGCTGTTGGTGCT NO: 2853 RAB6C NM_032144.1 GCGACAGCTCCTCTAGTTCCACCATGTCCGCGGGCGGAGACTTCGGGAATCCGCTGAGGAA SEQ ID ATTCAAGCTGGTGTTCC NO: 2854 RAC1 NM_006908.3 TGTTGTAAATGTCTCAGCCCCTCGTTCTTGGTCCTGTCCCTTGGAACCTTTGTACGCTTTGCTC SEQ ID AA NO: 2855 RAD51C NM_058216.1 GAACTTCTTGAGCAGGAGCATACCCAGGGCTTCATAATCACCTTCTGTTCAGCACTAGATGA SEQ ID TATTCTTGGGGGTGGA NO: 2856 RAD54L NM_003579.2 AGCTAGCCTCAGTGACACACATGACAGGTTGCACTGCCGACGTTGTGTCAACAGCCGTCAGA SEQ ID TCCGG NO: 2857 RAF1 NM_002880.1 CGTCGTATGCGAGAGTCTGTTTCCAGGATGCCTGTTAGTTCTCAGCACAGATATTCTACACCT SEQ ID CACGCCTTCA NO: 2858 RALBP1 NM_006788.2 GGTGTCAGATATAAATGTGCAAATGCCTTCTTGCTGTCCTGTCGGTCTCAGTACGTTCACTTT SEQ ID ATAGCTGCTGGCAATATCGAA NO: 2859 RANBP2 NM_006267.3 TCCTTCAGCTTTCACACTGGGCTCAGAAATGAAGTTGCATGACTCTTCTGGAAGTCAGGTGG SEQ ID GAACAGGATTT NO: 2860 ranBP7 NM_006391.1 AACATGATTATCCAAGCCGCTGGACTGCCATTGTGGACAAAATTGGCTTTTATCTTCAGTCC SEQ ID GATAACAGTGCTTGTTGGC NO: 2861 RANBP9 NM_005493.2 CAAGTCAGTTGAGACGCCAGTTGTGTGGAGGAAGTCAGGCCGCCATAGAAAGAATGATCCA SEQ ID CTTTGGACGAGAGCTGCA NO: 2862 RAP1GDS1 NM_021159.3 TGTGGATGCTGGATTGATTTCACCACTGGTGCAGCTGCTAAATAGCAAAGACCAGGAAGTGC SEQ ID TGCTT NO: 2863 RARA NM_000964.1 AGTCTGTGAGAAACGACCGAAACAAGAAGAAGAAGGAGGTGCCCAAGCCCGAGTGCTCTG SEQ ID AGAGCTACACGCTGACGCCG NO: 2864 RARB NM_016152.2 TGCCTGGACATCCTGATTCTTAGAATTTGCACCAGGTATACCCCAGAACAAGACACCATGAC SEQ ID TTTCTCAGACGGCCTT NO: 2865 RASSF1 NM_007182.3 AGTGGGAGACACCTGACCTTTCTCAAGCTGAGATTGAGCAGAAGATCAAGGAGTACAATGC SEQ ID CCAGATCA NO: 2866 RBM5 NM_005778.1 CGAGAGGGAGAGCAAGACCATCATGCTGCGCGGCCTTCCCATCACCATCACAGAGAGCGAT SEQ ID ATTCGAGA NO: 2867 RBX1 NM_014248.2 GGAACCACATTATGGATCTTTGCATAGAATGTCAAGCTAACCAGGCGTCCGCTACTTCAGAA SEQ ID GAGTGTACTGTCGCATG NO: 2868 RCC1 NM_001269.2 GGGCTGGGTGAGAATGTGATGGAGAGGAAGAAGCCGGCCCTGGTATCCATTCCGGAGGATG SEQ ID TTGTG NO: 2869 REG4 NM_032044.2 TGCTAACTCCTGCACAGCCCCGTCCTCTTCCTTTCTGCTAGCCTGGCTAAATCTGCTCATTAT SEQ ID TTCAGAGGGGAAACCTAGCA NO: 2870 RFC NM_003056.1 TCAAGACCATCATCACTTTCATTGTCTCGGACGTGCGGGGCCTGGGCCTCCCGGTCCGCAAG SEQ ID CAGTTCCAGTTATACTCCGTGTACTTCCTGATCC NO: 2871 RhoB NM_004040.2 AAGCATGAACAGGACTTGACCATCTTTCCAACCCCTGGGGAAGACATTTGCAACTGACTTGG SEQ ID GGAGG NO: 2872 rhoC NM_175744.1 CCCGTTCGGTCTGAGGAAGGCCGGGACATGGCGAACCGGATCAGTGCCTTTGGCTACCTTGA SEQ ID GTGCTC NO: 2873 RIZ1 NM_012231.1 CCAGACGAGCGATTAGAAGCGGCAGCTTGTGAGGTGAATGATTTGGGGGAAGAGGAGGAG SEQ ID GAGGAAGAGGAGGA NO: 2874 RNF11 NM_014372.3 ACCCTGGAAGAGATGGATCAGAAAAAAAGATCCGGGAGTGTGTGATCTGTATGATGGACTT SEQ ID TGTTTATGGGGACCCAAT NO: 2875 ROCK1 NM_005406.1 TGTGCACATAGGAATGAGCTTCAGATGCAGTTGGCCAGCAAAGAGAGTGATATTGAGCAAT SEQ ID TGCGTGCTAAAC NO: 2876 ROCK2 NM_004850.3 GATCCGAGACCCTCGCTCCCCCATCAACGTGGAGAGCTTGCTGGATGGCTTAAATTCCTTGG SEQ ID TCCT NO: 2877 RPLPO NM_001002.2 CCATTCTATCATCAACGGGTACAAACGAGTCCTGGCCTTGTCTGTGGAGACGGATTACACCT SEQ ID TCCCACTTGCTGA NO: 2878 RPS13 NM_001017.2 CAGTCGGCTTTACCCTATCGACGCAGCGTCCCCACTTGGTTGAAGTTGACATCTGACGACGT SEQ ID GAAGGAGCAGA NO: 2879 RRM1 NM_001033.1 GGGCTACTGGCAGCTACATTGCTGGGACTAATGGCAATTCCAATGGCCTTGTACCGATGCTG SEQ ID AGAG NO: 2880 RRM2 NM_001034.1 CAGCGGGATTAAACAGTCCTTTAACCAGCACAGCCAGTTAAAAGATGCAGCCTCACTGCTTC SEQ ID AACGCAGAT NO: 2881 RTN4 NM_007008.1 GACTGGAGTGGTGTTTGGTGCCAGCCTATTCCTGCTGCTTTCATTGACAGTATTCAGCATTGT SEQ ID GAGCGTAACAG NO: 2882 RUNX1 NM_001754.2 AACAGAGACATTGCCAACCATATTGGATCTGCTTGCTGTCCAAACCAGCAAACTTCCTGGGC SEQ ID AAATCAC NO: 2883 RXRA NM_002957.3 GCTCTGTTGTGTCCTGTTGCCGGCTCTGGCCTTCCTGTGACTGACTGTGAAGTGGCTTCTCCG SEQ ID TAC NO: 2884 S100A1 NM_006271.1 TGGACAAGGTGATGAAGGAGCTAGACGAGAATGGAGACGGGGAGGTGGACTTCCAGGAGT SEQ ID ATGTGGTGCT NO: 2885 S100A2 NM_005978.2 TGGCTGTGCTGGTCACTACCTTCCACAAGTACTCCTGCCAAGAGGGCGACAAGTTCAAGCTG SEQ ID AGTAAGGGGGA NO: 2886 S100A4 NM_002961.2 GACTGCTGTCATGGCGTGCCCTCTGGAGAAGGCCCTGGATGTGATGGTGTCCACCTTCCACA SEQ ID AGTACTCG NO: 2887 S100A8 NM_002964.3 ACTCCCTGATAAAGGGGAATTTCCATGCCGTCTACAGGGATGACCTGAAGAAATTGCTAGA SEQ ID GACCGAGTGTCCTCA NO: 2888 S100A9 NM_002965.2 CTTTGGGACAGAGTGCAAGACGATGACTTGCAAAATGTCGCAGCTGGAACGCAACATAGAG SEQ ID ACCA NO: 2889 S100P NM_005980.2 AGACAAGGATGCCGTGGATAAATTGCTCAAGGACCTGGACGCCAATGGAGATGCCCAGGTG SEQ ID GACTTC NO: 2890 SAT NM_002970.1 CCTTTTACCACTGCCTGGTTGCAGAAGTGCCGAAAGAGCACTGGACTCCGGAAGGACACAG SEQ ID CATTGT NO: 2891 SBA2 NM_018639.3 GGACTCAACGATGGGCAGATCAAGATCTGGGAGGTGCAGACAGGGCTCCTGCTTTTGAATC SEQ ID TTTCCG NO: 2892 SDC1 NM_002997.1 GAAATTGACGAGGGGTGTCTTGGGCAGAGCTGGCTCTGAGCGCCTCCATCCAAGGCCAGGT SEQ ID TCTCCGTTAGCTCCT NO: 2893 SEMA3B NM_004636.1 GCTCCAGGATGTGTTTCTGTTGTCCTCGCGGGACCACCGGACCCCGCTGCTCTATGCCGTCTT SEQ ID CTCCACGT NO: 2894 SEMA3F NM_004186.1 CGCGAGCCCCTCATTATACACTGGGCAGCCTCCCCACAGCGCATCGAGGAATGCGTGCTCTC SEQ ID AGGCAAGGATGTCAACGGCGAGTG NO: 2895 SEMA4B NM_020210.1 TTCCAGCCCAACACAGTGAACACTTTGGCCTGCCCGCTCCTCTCCAACCTGGCGACCCGACTC SEQ ID NO: 2896 SFRP2 NM_003013.2 CAAGCTGAACGGTGTGTCCGAAAGGGACCTGAAGAAATCGGTGCTGTGGCTCAAAGACAGC SEQ ID TTGCA NO: 2897 SFRP4 NM_003014.2 TACAGGATGAGGCTGGGCATTGCCTGGGACAGCCTATGTAAGGCCATGTGCCCCTTGCCCTA SEQ ID ACAAC NO: 2898 SGCB NM_000232.1 CAGTGGAGACCAGTTGGGTAGTGGTGACTGGGTACGCTACAAGCTCTGCATGTGTGCTGATG SEQ ID GGACGCTCTTCAAGG NO: 2899 SHC1 NM_003029.3 CCAACACCTTCTTGGCTTCTGGGACCTGTGTTCTTGCTGAGCACCCTCTCCGGTTTGGGTTGG SEQ ID GATAACAG NO: 2900 SHH NM_000193.2 GTCCAAGGCACATATCCACTGCTCGGTGAAAGCAGAGAACTCGGTGGCGGCCAAATCGGGA SEQ ID GGCTGCTTC NO: 2901 SI NM_001041.1 AACGGACTCCCTCAATTTGTGCAAGATTTGCATGACCATGGACAGAAATATGTCATCATCTT SEQ ID GGACCCTGCAATTTC NO: 2902 Siah-1 NM_003031.2 TTGGCATTGGAACTACATTCAATCCGCGGTATCCTCGGATTAGTTCTAGGACCCCCTTCTCCA SEQ ID TACC NO: 2903 SIAT4A NM_003033.2 AACCACAGTTGGAGGAGGACGGCAGAGACAGTTTCCCTCCCCGCTATACCAACACCCTTCCT SEQ ID TCG NO: 2904 SIAT7B NM_006456.1 TCCAGCCCAAATCCTCCTGGTGGCACATCCTACCCCAGATGCTAAAGTGATTCAAGGACTCC SEQ ID AGGACACC NO: 2905 SIM2 NM_005069.2 GATGGTAGGAAGGGATGTGCCCGCCTCTCCACGCACTCAGCTATACCTCATTCACAGCTCCT SEQ ID TGTG NO: 2906 SIN3A NM_015477.1 CCAGAGTCATGCTCATCCAGCCCCACCAGTTGCACCAGTGCAGGGACAGCAGCAATTTCAG SEQ ID AGGCTGAAGGTGG NO: 2907 SIR2 NM_012238.3 AGCTGGGGTGTCTGTTTCATGTGGAATACCTGACTTCAGGTCAAGGGATGGTATTTATGCTC SEQ ID GCCTTGCTGT NO: 2908 SKP1A NM_006930.2 CCATTGCCTTTGCTTTGTTCATAATTTCAGCAGGGCAGAATAAAAACCATGGGAGGCAAAGA SEQ ID AAGGAAATCCGGAA NO: 2909 SKP2 NM_005983.2 AGTTGCAGAATCTAAGCCTGGAAGGCCTGCGGCTTTCGGATCCCATTGTCAATACTCTCGCA SEQ ID AAAAACTCA NO: 2910 SLC25A3 NM_213611.1 TCTGCCAGTGCTGAATTCTTTGCTGACATTGCCCTGGCTCCTATGGAAGCTGCTAAGGTTCGAA SEQ ID NO: 2911 SLC2A1 NM_006516.1 GCCTGAGTCTCCTGTGCCCACATCCCAGGCTTCACCCTGAATGGTTCCATGCCTGAGGGTGG SEQ ID AGACT NO: 2912 SLC31A1 NM_001859.2 CCGTTCGAAGAGTCGTGAGGGGGTGACGGGTTAAGATTCGGAGAGAGAGGTGCTAGTGGCT SEQ ID GGACT NO: 2913 SLC5A8 NM_145913.2 CCTGCTTTCAACCACATTGAATTGAACTCAGATCAGAGTGGCAAGAGCAATGGGACTCGTTT SEQ ID GTGAAGCTGCTCT NO: 2914 SLC7A5 NM_003486.4 GCGCAGAGGCCAGTTAAAGTAGATCACCTCCTCGAACCCACTCCGGTTCCCCGCAACCCACA SEQ ID GCTCAGCT NO: 2915 SLPI NM_003064.2 ATGGCCAATGTTTGATGCTTAACCCCCCCAATTTCTGTGAGATGGATGGCCAGTGCAAGCGT SEQ ID GACTTGAAGTGT NO: 2916 SMARCA3 NM_003071.2 AGGGACTGTCCTGGCACATTATGCAGATGTCCTGGGTCTTTTGCTTAGACTGCGGCAAATTT SEQ ID GTTG NO: 2917 SNAI1 NM_005985.2 CCCAATCGGAAGCCTAACTACAGCGAGCTGCAGGACTCTAATCCAGAGTTTACCTTCCAGCA SEQ ID GCCCTAC NO: 2918 SNAI2 NM_003068.3 GGCTGGCCAAACATAAGCAGCTGCACTGCGATGCCCAGTCTAGAAAATCTTTCAGCTGTAAA SEQ ID TACTGTGACAAGGA NO: 2919 SNRPF NM_003095.1 GGCTGGTCGGCAGAGAGTAGCCTGCAACATTCGGCCGTGGTTTACATGAGTTTACCCCTCAA SEQ ID TCCCAAACCTTTCCTCA NO: 2920 SOD1 NM_000454.3 TGAAGAGAGGCATGTTGGAGACTTGGGCAATGTGACTGCTGACAAAGATGGTGTGGCCGAT SEQ ID GTGTCTATT NO: 2921 SOD2 NM_000636.1 GCTTGTCCAAATCAGGATCCACTGCAAGGAACAACAGGCCTTATTCCACTGCTGGGGATTGA SEQ ID TGTGTGGGAGCACGCT NO: 2922 SOS1 NM_005633.2 TCTGCACCAAATTCTCCAAGAACACCGTTAACACCTCCGCCTGCTTCTGGTGCTTCCAGTACC SEQ ID AC NO: 2923 SOX17 NM_022454.2 TCGTGTGCAAGCCTGAGATGGGCCTCCCCTACCAGGGGCATGACTCCGGTGTGAATCTCCCC SEQ ID GACAG NO: 2924 SPARC NM_003118.1 TCTTCCCTGTACACTGGCAGTTCGGCCAGCTGGACCAGCACCCCATTGACGGGTACCTCTCC SEQ ID CACACCGAGCT NO: 2925 SPINT2 NM_021102.1 AGGAATGCAGCGGATTCCTCTGTCCCAAGTGCTCCCAGAAGGCAGGATTCTGAAGACCACTC SEQ ID CAGCGA NO: 2926 SPRY1 AK026960.1 CAGACCAGTCCCTGGTCATAGGTCTGAAAGGGCAATCCGGACCCAGCCCAAGCAACTGATT SEQ ID GTGGATGACTTGAAGG NO: 2927 SPRY2 NM_005842.1 TGTGGCAAGTGCAAATGTAAGGAGTGCACCTACCCAAGGCCTCTGCCATCAGACTGGATCTG SEQ ID CGAC NO: 2928 SR-A1 NM_021228.1 AGATGGAAGAAGCCAACCTGGCGAGCCGAGCGAAGGCCCAGGAGCTGATCCAGGCCACCA SEQ ID ACCAGATCCTCAGCCACAG NO: 2929 ST14 NM_021978.2 TGACTGCACATGGAACATTGAGGTGCCCAACAACCAGCATGTGAAGGTGCGCTTCAAATTCTT SEQ ID NO: 2930 STAT1 NM_007315.1 GGGCTCAGCTTTCAGAAGTGCTGAGTTGGCAGTTTTCTTCTGTCACCAAAAGAGGTCTCAAT SEQ ID GTGGACCAGCTGAACATGT NO: 2931 STAT3 NM_003150.1 TCACATGCCACTTTGGTGTTTCATAATCTCCTGGGAGAGATTGACCAGCAGTATAGCCGCTT SEQ ID CCTGCAAG NO: 2932 STAT5A NM_003152.1 GAGGCGCTCAACATGAAATTCAAGGCCGAAGTGCAGAGCAACCGGGGCCTGACCAAGGAG SEQ ID AACCTCGTGTTCCTGGC NO: 2933 STAT5B NM_012448.1 CCAGTGGTGGTGATCGTTCATGGCAGCCAGGACAACAATGCGACGGCCACTGTTCTCTGGGA SEQ ID CAATGCTTTTGC NO: 2934 STC1 NM_003155.1 CTCCGAGGTGAGGAGGACTCTCCCTCCCACATCAAACGCACATCCCATGAGAGTGCATAACC SEQ ID AGGGAGAGGT NO: 2935 STK11 NM_000455.3 GGACTCGGAGACGCTGTGCAGGAGGGCCGTCAAGATCCTCAAGAAGAAGAAGTTGCGAAG SEQ ID GATCCC NO: 2936 STK15 NM_003600.1 CATCTTCCAGGAGGACCACTCTCTGTGGCACCCTGGACTACCTGCCCCCTGAAATGATTGAA SEQ ID GGTCGGA NO: 2937 STMN1 NM_005563.2 AATACCCAACGCACAAATGACCGCACGTTCTCTGCCCCGTTTCTTGCCCCAGTGTGGTTTGC SEQ ID ATTGTCTCC NO: 2938 STMY3 NM_005940.2 CCTGGAGGCTGCAACATACCTCAATCCTGTCCCAGGCCGGATCCTCCTGAAGCCCTTTTCGC SEQ ID AGCACTGCTATCCTCCAAAGCCATTGTA NO: 2939 STS NM_000351.2 GAAGATCCCTTTCCTCCTACTGTTCTTTCTGTGGGAAGCCGAGAGCCACGAAGCATCAAGGC SEQ ID CGAACATCATCC NO: 2940 SURV NM_001168.1 TGTTTTGATTCCCGGGCTTACCAGGTGAGAAGTGAGGGAGGAAGAAGGCAGTGTCCCTTTTG SEQ ID CTAGAGCTGACAGCTTTG NO: 2941 TAGLN NM_003186.2 GATGGAGCAGGTGGCTCAGTTCCTGAAGGCGGCTGAGGACTCTGGGGTCATCAAGACTGAC SEQ ID ATGTTCCAGACT NO: 2942 TBP NM_003194.1 GCCCGAAACGCCGAATATAATCCCAAGCGGTTTGCTGCGGTAATCATGAGGATAAGAGAGC SEQ ID CACG NO: 2943 TCF-1 NM_000545.3 GAGGTCCTGAGCACTGCCAGGAGGGACAAAGGAGCCTGTGAACCCAGGACAAGCATGGTCC SEQ ID CACATC NO: 2944 TCF-7 NM_003202.2 GCAGCTGCAGTCAACAGTTCAAAGAAGTCATGGCCCAAATCCAGTGTGCACCCCTCCCCATT SEQ ID CACAG NO: 2945 TCF7L1 NM_031283.1 CCGGGACACTTTCCAGAAGCCGCGGGACTATTTCGCCGAAGTGAGAAGGCCTCAGGACAGC SEQ ID GCGTTCT NO: 2946 TCF7L2 NM_030756.1 CCAATCACGACAGGAGGATTCAGACACCCCTACCCCACAGCTCTGACCGTCAATGCTTCCGT SEQ ID GTCCA NO: 2947 TCFL4 NM_170607.2 CTGACTGCTCTGCTTAAAGGTGAAAGTAGCAGGAACAACAACAAAAGCCAACCAAAAACAA SEQ ID GGTAGCCAGTGCAAGACAT NO: 2948 TEK NM_000459.1 ACTTCGGTGCTACTTAACAACTTACATCCCAGGGAGCAGTACGTGGTCCGAGCTAGAGTCAA SEQ ID CACCAAGGCCCAGG NO: 2949 TERC U86046.1 AAGAGGAACGGAGCGAGTCCCCGCGCGCGGCGCGATTCCCTGAGCTGTGGGACGTGCACCC SEQ ID AGGACTCGGCTCACACAT NO: 2950 TERT NM_003219.1 GACATGGAGAACAAGCTGTTTGCGGGGATTCGGCGGGACGGGCTGCTCCTGCGTTTGGTGG SEQ ID ATGATTTCTTGTTGGTGACACCTC NO: 2951 TFF3 NM_003226.1 AGGCACTGTTCATCTCAGTTTTTCTGTCCCTTTGCTCCCGGCAAGCTTTCTGCTGAAAGTTCA SEQ ID TATCTGGAGCCTGATG NO: 2952 TGFA NM_003236.1 GGTGTGCCACAGACCTTCCTACTTGGCCTGTAATCACCTGTGCAGCCTTTTGTGGGCCTTCAA SEQ ID AACTCTGTCAAGAACTCCGT NO: 2953 TGFB2 NM_003238.1 ACCAGTCCCCCAGAAGACTATCCTGAGCCCGAGGAAGTCCCCCCGGAGGTGATTTCCATCTA SEQ ID CAACAGCACCAGG NO: 2954 TGFB3 NM_003239.1 GGATCGAGCTCTTCCAGATCCTTCGGCCAGATGAGCACATTGCCAAACAGCGCTATATCGGT SEQ ID GGC NO: 2955 TGFBI NM_000358.1 GCTACGAGTGCTGTCCTGGATATGAAAAGGTCCCTGGGGAGAAGGGCTGTCCAGCAGCCCT SEQ ID ACCACT NO: 2956 TGFBR1 NM_004612.1 GTCATCACCTGGCCTTGGTCCTGTGGAACTGGCAGCTGTCATTGCTGGACCAGTGTGCTTCGT SEQ ID CTGC NO: 2957 TGFBR2 NM_003242.2 AACACCAATGGGTTCCATCTTTCTGGGCTCCTGATTGCTCAAGCACAGTTTGGCCTGATGAA SEQ ID GAGG NO: 2958 THBS1 NM_003246.1 CATCCGCAAAGTGACTGAAGAGAACAAAGAGTTGGCCAATGAGCTGAGGCGGCCTCCCCTA SEQ ID TGCTATCACAACGGAGTTCAGTAC NO: 2959 THY1 NM_006288.2 GGACAAGACCCTCTCAGGCTGTCCCAAGCTCCCAAGAGCTTCCAGAGCTCTGACCCACAGCC SEQ ID TCCAA NO: 2960 TIMP1 NM_003254.1 TCCCTGCGGTCCCAGATAGCCTGAATCCTGCCCGGAGTGGAACTGAAGCCTGCACAGTGTCC SEQ ID ACCCTGTTCCCAC NO: 2961 TIMP2 NM_003255.2 TCACCCTCTGTGACTTCATCGTGCCCTGGGACACCCTGAGCACCACCCAGAAGAAGAGCCTG SEQ ID AACCACA NO: 2962 TIMP3 NM_000362.2 CTACCTGCCTTGCTTTGTGACTTCCAAGAACGAGTGTCTCTGGACCGACATGCTCTCCAATTT SEQ ID CGGT NO: 2963 TJP1 NM_003257.1 ACTTTGCTGGGACAAAGGTCAACTGAAGAAGTGGGCAGGCCCGAGGCAGGAGAGATGCTGA SEQ ID GGAGTCCATGTG NO: 2964 TK1 NM_003258.1 GCCGGGAAGACCGTAATTGTGGCTGCACTGGATGGGACCTTCCAGAGGAAGCCATTTGGGG SEQ ID CCATCCTGAACCTGGTGCCGCTG NO: 2965 TLN1 NM_006289.2 AAGCAGAAGGGAGAGCGTAAGATCTTCCAGGCACACAAGAATTGTGGGCAGATGAGTGAG SEQ ID ATTGAGGCCAAGG NO: 2966 TMEPAI NM_020182.3 CAGAAGGATGCCTGTGGCCCTCGGAGAGCACAGTGTCAGGCAACGGAATCCCAGAGCCGCA SEQ ID GGTCTAC NO: 2967 TMSB10 NM_021103.2 GAAATCGCCAGCTTCGATAAGGCCAAGCTGAAGAAAACGGAGACGCAGGAAAAGAACACC SEQ ID CTGCCGAC NO: 2968 TMSB4X NM_021109.2 CACATCAAAGAACTACTGACAACGAAGGCCGCGCCTGCCTTTCCCATCTGTCTATCTATCTG SEQ ID GCTGGCAGG NO: 2969 TNC NM_002160.1 AGCTCGGAACCTCACCGTGCCTGGCAGCCTTCGGGCTGTGGACATACCGGGCCTCAAGGCTG SEQ ID CTAC NO: 2970 TNF NM_000594.1 GGAGAAGGGTGACCGACTCAGCGCTGAGATCAATCGGCCCGACTATCTCGACTTTGCCGAG SEQ ID TCTGGGCA NO: 2971 TNFRSF5 NM_001250.3 TCTCACCTCGCTATGGTTCGTCTGCCTCTGCAGTGCGTCCTCTGGGGCTGCTTGCTGACCGCT SEQ ID GTCCATC NO: 2972 TNFRSF6B NM_003823.2 CCTCAGCACCAGGGTACCAGGAGCTGAGGAGTGTGAGCGTGCCGTCATCGACTTTGTGGCTT SEQ ID TCCAGGACA NO: 2973 TNFSF4 NM_003326.2 CTTCATCTTCCCTCTACCCAGATTGTGAAGATGGAAAGGGTCCAACCCCTGGAAGAGAATGT SEQ ID GGGAAATGCAGC NO: 2974 TOP2A NM_001067.1 AATCCAAGGGGGAGAGTGATGACTTCCATATGGACTTTGACTCAGCTGTGGCTCCTCGGGCA SEQ ID AAATCTGTAC NO: 2975 TOP2B NM_001068.1 TGTGGACATCTTCCCCTCAGACTTCCCTACTGAGCCACCTTCTCTGCCACGAACCGGTCGGGC SEQ ID TAG NO: 2976 TP NM_001953.2 CTATATGCAGCCAGAGATGTGACAGCCACCGTGGACAGCCTGCCACTCATCACAGCCTCCAT SEQ ID TCTCAGTAAGAAACTCGTGG NO: 2977 TP53BP1 NM_005657.1 TGCTGTTGCTGAGTCTGTTGCCAGTCCCCAGAAGACCATGTCTGTGTTGAGCTGTATCTGTGA SEQ ID AGCCAGGCAAG NO: 2978 TP53BP2 NM_005426.1 GGGCCAAATATTCAGAAGCTTTTATATCAGAGGACCACCATAGCGGCCATGGAGACCATCTC SEQ ID TGTCCCATCATACCCATCC NO: 2979 TP53I3 NM_004881.2 GCGGACTTAATGCAGAGACAAGGCCAGTATGACCCACCTCCAGGAGCCAGCAACATTTTGG SEQ ID GACTTGA NO: 2980 TRAG3 NM_004909.1 GACGCTGGTCTGGTGAAGATGTCCAGGAAACCACGAGCCTCCAGCCCATTGTCCAACAACC SEQ ID ACCCA NO: 2981 TRAIL NM_003810.1 CTTCACAGTGCTCCTGCAGTCTCTCTGTGTGGCTGTAACTTACGTGTACTTTACCAACGAGCT SEQ ID GAAGCAGATG NO: 2982 TS NM_001071.1 GCCTCGGTGTGCCTTTCAACATCGCCAGCTACGCCCTGCTCACGTACATGATTGCGCACATC SEQ ID ACG NO: 2983 TST NM_003312.4 GGAGCCGGATGCAGTAGGACTGGACTCGGGCCATATCCGTGGTGCCGTCAACATGCCTTTCA SEQ ID TGGACTT NO: 2984 TUBA1 NM_006000.1 TGTCACCCCGACTCAACGTGAGACGCACCGCCCGGACTCACCATGCGTGAATGCATCTCAGT SEQ ID CCACGT NO: 2985 TUBB NM_001069.1 CGAGGACGAGGCTTAAAAACTTCTCAGATCAATCGTGCATCCTTAGTGAACTTCTGTTGTCC SEQ ID TCAAGCATGGT NO: 2986 TUFM NM_003321.3 GTATCACCATCAATGCGGCTCATGTGGAGTATAGCACTGCCGCCCGCCACTACGCCCACACA SEQ ID GACTG NO: 2987 TULP3 NM_003324.2 TGTGTATAGTCCTGCCCCTCAAGGTGTCACAGTAAGATGTCGGATAATCCGGGATAAAAGGG SEQ ID GAATGGATCGGG NO: 2988 tusc4 NM_006545.4 GGAGGAGCTAAATGCCTCAGGCCGGTGCACTCTGCCCATTGATGAGTCCAACACCATCCACT SEQ ID TGAAGG NO: 2989 UBB NM_018955.1 GAGTCGACCCTGCACCTGGTCCTGCGTCTGAGAGGTGGTATGCAGATCTTCGTGAAGACCCT SEQ ID GACCGGCAAGACCATCACCCTGGAAGTGGAGCCCAGTGACACCATCGAAAATGTGAAGGCC NO: AAGATCCAGGATAAAGAAGGCATCCCTCCCGACCAGCAGAGGCTCATCTTTGCAGGCAAGC 2990 AGCTGGAAGATGGCCGCACTCTTTCTGACTACAACATCCAGAAGGAGTCGACCCTGCACCTG GTCCTGCGTCTGAGAGGTGGTATGCAGATCTTCGTGAAGACCCTGACCGGCAAGACCATCAC TCTGGAAGTGGAGCCCAGTGACACCATCGAAAATGTGAAGGCCAAGATCCAAGATAAAGAA GGCATCCCTCCCGACCAGCAGAGGCTCATCTTTGCAGGCAAGCAGCTGGAAGATGGCCGCA CTCTTTCTGACTACAACATCCAGAAGGAGTCGACCCTGCACCTGGTCCTGCGCCTGAGGGGT GGCTGTTAATTCTTCAGTCATGGCATTCGC UBC NM_021009.2 ACGCACCCTGTCTGACTACAACATCCAGAAAGAGTCCACCCTGCACCTGGTGCTCCGTCTTA SEQ ID GAGGT NO: 2991 UBE2C NM_007019.2 TGTCTGGCGATAAAGGGATTTCTGCCTTCCCTGAATCAGACAACCTTTTCAAATGGGTAGGG SEQ ID ACCAT NO: 2992 UBE2M NM_003969.1 CTCCATAATTTATGGCCTGCAGTATCTCTTCTTGGAGCCCAACCCCGAGGACCCACTGAACA SEQ ID AGGAGGCCGCA NO: 2993 UBL1 NM_003352.3 GTGAAGCCACCGTCATCATGTCTGACCAGGAGGCAAAACCTTCAACTGAGGACTTGGGGGA SEQ ID TAAGAAGGAAGG NO: 2994 UCP2 NM_003355.2 ACCATGCTCCAGAAGGAGGGGCCCCGAGCCTTCTACAAAGGGTTCATGCCCTCCTTTCTCCG SEQ ID CTTGGGTT NO: 2995 UGT1A1 NM_000463.2 CCATGCAGCCTGGAATTTGAGGCTACCCAGTGCCCCAACCCATTCTCCTACGTGCCCAGGCC SEQ ID TCTC NO: 2996 UMPS NM_000373.1 TGCGGAAATGAGCTCCACCGGCTCCCTGGCCACTGGGGACTACACTAGAGCAGCGGTTAGA SEQ ID ATGGCTGAGG NO: 2997 UNC5A XM_030300.7 GACAGCTGATCCAGGAGCCACGGGTCCTGCACTTCAAGGACAGTTACCACAACCTGCGCCT SEQ ID ATCCAT NO: 2998 UNC5B NM_170744.2 AGAACGGAGGCCGTGACTGCAGCGGGACGCTGCTCGACTCTAAGAACTGCACAGATGGGCT SEQ ID GTGCATG NO: 2999 UNC5C NM_003728.2 CTGAACACAGTGGAGCTGGTTTGCAAACTCTGTGTGCGGCAGGTGGAAGGAGAAGGGCAGA SEQ ID TCTTCCAG NO: 3000 upa NM_002658.1 GTGGATGTGCCCTGAAGGACAAGCCAGGCGTCTACACGAGAGTCTCACACTTCTTACCCTGG SEQ ID ATCCGCAG NO: 3001 UPP1 NM_003364.2 ACGGGTCCTGCCTCAGTTGGCGGAATGGCGGCCACGGGAGCCAATGCAGAGAAAGCTGAAA SEQ ID GTCACAATGATTGCCCCG NO: 3002 VCAM1 NM_001078.2 TGGCTTCAGGAGCTGAATACCCTCCCAGGCACACACAGGTGGGACACAAATAAGGGTTTTG SEQ ID GAACCACTATTTTCTCATCACGACAGCA NO: 3003 VCL NM_003373.2 GATACCACAACTCCCATCAAGCTGTTGGCAGTGGCAGCCACGGCGCCTCCTGATGCGCCTAA SEQ ID CAGGGA NO: 3004 VCP NM_007126.2 GGCTTTGGCAGCTTCAGATTCCCTTCAGGGAACCAGGGTGGAGCTGGCCCCAGTCAGGGCA SEQ ID GTGGAG NO: 3005 VDAC1 NM_003374.1 GCTGCGACATGGATTTCGACATTGCTGGGCCTTCCATCCGGGGTGCTCTGGTGCTAGGTTAC SEQ ID GAGGGCTGG NO: 3006 VDAC2 NM_003375.2 ACCCACGGACAGACTTGCGCGCGTCCAATGTGTATTCCTCCATCATATGCTGACCTTGGCAA SEQ ID AGCT NO: 3007 VDR NM_000376.1 GCCCTGGATTTCAGAAAGAGCCAAGTCTGGATCTGGGACCCTTTCCTTCCTTCCCTGGCTTGT SEQ ID AACT NO: 3008 VEGF NM_003376.3 CTGCTGTCTTGGGTGCATTGGAGCCTTGCCTTGCTGCTCTACCTCCACCATGCCAAGTGGTCC SEQ ID CAGGCTGC NO: 3009 VEGF_altsplice1 AF486837.1 TGTGAATGCAGACCAAAGAAAGATAGAGCAAGACAAGAAAATCCCTGTGGGCCTTGCTCAG SEQ ID AGCGGAGAAAGC NO: 3010 VEGF_altsplice2 AF214570.1 AGCTTCCTACAGCACAACAAATGTGAATGCAGACCAAAGAAAGATAGAGCAAGACAAGAA SEQ ID AAATGTGACAAGCCGAG NO: 3011 VEGFB NM_003377.2 TGACGATGGCCTGGAGTGTGTGCCCACTGGGCAGCACCAAGTCCGGATGCAGATCCTCATG SEQ ID ATCCGGTACC NO: 3012 VEGFC NM_005429.2 CCTCAGCAAGACGTTATTTGAAATTACAGTGCCTCTCTCTCAAGGCCCCAAACCAGTAACAA SEQ ID TCAGTTTTGCCAATCACACTT NO: 3013 VIM NM_003380.1 TGCCCTTAAAGGAACCAATGAGTCCCTGGAACGCCAGATGCGTGAAATGGAAGAGAACTTT SEQ ID GCCGTTGAAGC NO: 3014 WIF NM_007191.2 TACAAGCTGAGTGCCCAGGCGGGTGCCGAAATGGAGGCTTTTGTAATGAAAGACGCATCTG SEQ ID CGAGTG NO: 3015 WISP1 NM_003882.2 AGAGGCATCCATGAACTTCACACTTGCGGGCTGCATCAGCACACGCTCCTATCAACCCAAGT SEQ ID ACTGTGGAGTTTG NO: 3016 Wnt-3a NM_033131.2 ACAAAGCTACCAGGGAGTCGGCCTTTGTCCACGCCATTGCCTCAGCCGGTGTGGCCTTTGCA SEQ ID GTGACACGCTCA NO: 3017 Wnt-5a NM_003392.2 GTATCAGGACCACATGCAGTACATCGGAGAAGGCGCGAAGACAGGCATCAAAGAATGCCA SEQ ID GTATCAATTCCGACA NO: 3018 Wnt-5b NM_032642.2 TGTCTTCAGGGTCTTGTCCAGAATGTAGATGGGTTCCGTAAGAGGCCTGGTGCTCTCTTACTC SEQ ID TTTCATCCACGTGCAC NO: 3019 WNT2 NM_003391.1 CGGTGGAATCTGGCTCTGGCTCCCTCTGCTCTTGACCTGGCTCACCCCCGAGGTCAACTCTTC SEQ ID ATGG NO: 3020 WWOX NM_016373.1 ATCGCAGCTGGTGGGTGTACACACTGCTGTTTACCTTGGCGAGGCCTTTCACCAAGTCCATG SEQ ID CAACAGGGAGCT NO: 3021 XPA NM_000380.2 GGGTAGAGGGAAAAGGGTTCAACAAAGGCTGAACTGGATTCTTAACCAAGAAACAAATAAT SEQ ID AGCAATGGTGGTGCA NO: 3022 XPC NM_004628.2 GATACATCGTCTGCGAGGAATTCAAAGACGTGCTCCTGACTGCCTGGGAAAATGAGCAGGC SEQ ID AGTCATTGAAAG NO: 3023 XRCC1 NM_006297.1 GGAGATGAAGCCCCCAAGCTTCCTCAGAAGCAACCCCAGACCAAAACCAAGCCCACTCAGG SEQ ID CAGCTGGAC NO: 3024 YB-1 NM_004559.1 AGACTGTGGAGTTTGATGTTGTTGAAGGAGAAAAGGGTGCGGAGGCAGCAAATGTTACAGG SEQ ID TCCTGGTGGTGTTCC NO: 3025 YWHAH NM_003405.2 CATGGCCTCCGCTATGAAGGCGGTGACAGAGCTGAATGAACCTCTCTCCAATGAAGATCGA SEQ ID AATCTCC NO: 3026 zbtb7 NM_015898.2 CTGCGTTCACACCCCAGTGTCACAGGGCGAGCTGTTCTGGAGAGAAAACCATCTGTCGTGGC SEQ ID TGAG NO: 3027 ZG16 NM_152338.1 TGCTGAGCCTCCTCTCCTTGGCAGGGGCACTGTGATGAGGAGTAAGAACTCCCTTATCACTA SEQ ID ACCCCCATCC NO: 3028

TABLE 4 Most Highly Correlated Genes Variable Rank 1 Rank 2 Rank 3 Rank 4 Rank 5 Rank 6 Rank 7 Rank 8 Rank 9 Rank 10 ADAMTS12 SPARC TIMP2 COL1A1 ANTXR1 BGN LOXL2 THY1 CDH11 IGFBP7 COL1A2 0.7317 0.7177 0.7077 0.7022 0.6962 0.6679 0.6665 0.647 0.6433 0.6393 ANTXR1 TIMP2 BGN COL1A1 THY1 FAP SFRP4 SPARC TGFB3 ADAMTS12 PDGFC 0.8358 0.8159 0.7796 0.7696 0.7261 0.7154 0.7138 0.7119 0.7022 0.6992 BGN COL1A1 SPARC TIMP2 FAP ANTXR1 TGFB3 SFRP2 INHBA WISP1 CTHRC1 0.8986 0.8711 0.8446 0.8177 0.8159 0.8147 0.811 0.7854 0.7682 0.7668 CALD1 IGFBP5 TAGLN CDH11 TIMP2 MYLK PDGFC DLC1 ANTXR1 IGFBP7 SPARC 0.7483 0.7452 0.7339 0.691 0.6846 0.6822 0.6707 0.6524 0.6494 0.649 CDH11 SPARC TIMP2 IGFBP7 CALD1 TAGLN IGFBP5 COL1A2 BGN MMP2 PDGFC 0.7831 0.7629 0.7587 0.7339 0.7338 0.7319 0.7272 0.7265 0.7019 0.6845 COL1A1 BGN SPARC TIMP2 FAP ANTXR1 LOXL2 COL1A2 CTHRC1 TGFB3 WISP1 0.8986 0.8713 0.8071 0.7833 0.7796 0.7724 0.7642 0.7496 0.7491 0.7442 COL1A2 SPARC MMP2 COL1A1 THBS1 BGN CDH11 LOXL2 ITGA5 CTHRC1 INHBA 0.8549 0.7886 0.7642 0.7409 0.7368 0.7272 0.7248 0.7243 0.7112 0.7005 CTGF CYR61 THBS1 INHBA BGN COL1A2 SPARC PAI1 VIM SFRP2 CXCL12 0.8028 0.7694 0.7078 0.6912 0.6893 0.6886 0.6763 0.6747 0.6688 0.6683 CTHRC1 FAP BGN COL1A1 INHBA COL1A2 TIMP3 SFRP2 SPARC TIMP2 LOXL2 0.7713 0.7668 0.7496 0.7348 0.7112 0.7078 0.699 0.6964 0.6853 0.67 CTSL TP SOD2 ITGA5 UPA TIMP1 THBS1 PAI1 COL1A2 DPYD CD68 0.6975 0.6913 0.6748 0.6558 0.6448 0.636 0.6296 0.6152 0.6151 0.6148 CXCL12 BGN CTGF SFRP2 TIMP2 TGFB3 VIM COL1A1 SPARC CYR61 MCP1 0.6838 0.6683 0.6649 0.6334 0.6254 0.6212 0.6206 0.6173 0.6149 0.6022 CYR61 CTGF DUSP1 THBS1 PAI1 COL1A2 INHBA CXCL12 CTHRC1 VIM GADD45B 0.8028 0.7338 0.6623 0.6477 0.6272 0.6257 0.6149 0.5918 0.576 0.573 DLC1 TIMP2 CALD1 IGFBP5 TGFB3 BGN ANTXR1 TAGLN THY1 HSPG2 TLN1 0.6783 0.6707 0.653 0.6465 0.6399 0.6378 0.6075 0.6065 0.6047 0.5982 DUSP1 CYR61 FOS CTGF PAI1 EGR1 NR4A1 GADD45B THBS1 CXCL12 EGR3 0.7338 0.7183 0.6632 0.6545 0.6357 0.5993 0.5877 0.5827 0.5262 0.5184 FAP BGN COL1A1 CTHRC1 TIMP2 INHBA ANTXR1 SFRP2 WISP1 TIMP3 TGFB3 0.8177 0.7833 0.7713 0.7364 0.7286 0.7261 0.7189 0.7147 0.7027 0.7001 HSPG2 TIMP2 THY1 IGFBP7 SPARC TAGLN ANTXR1 BGN IGFBP5 COL1A1 CDH11 0.7455 0.7425 0.7246 0.6959 0.6857 0.6678 0.6625 0.6259 0.608 0.6052 IGFBP5 TAGLN IGFBP7 CALD1 CDH11 TIMP2 SPARC MYLK DLC1 TIMP1 BGN 0.7829 0.764 0.7483 0.7319 0.6893 0.6781 0.6532 0.653 0.6403 0.6374 IGFBP7 TAGLN SPARC IGFBP5 CDH11 THY1 HSPG2 TIMP2 SFRP4 ANTXR1 PDGFC 0.8225 0.7715 0.764 0.7587 0.7428 0.7246 0.7139 0.6558 0.6541 0.6538 INHBA BGN SPARC CTHRC1 FAP COL1A1 CTGF COL1A2 CDH11 THBS1 LOXL2 0.7854 0.774 0.7348 0.7286 0.7202 0.7078 0.7005 0.6744 0.6685 0.6613 ITGA5 COL1A2 THBS1 MMP2 SPARC CTSL PAI1 TIMP1 UPA NRP2 SNAI2 0.7243 0.7058 0.6969 0.6772 0.6748 0.671 0.6374 0.6357 0.6301 0.623 LOXL2 COL1A1 SPARC BGN COL1A2 TIMP2 ANTXR1 CTHRC1 ADAMTS12 INHBA FAP 0.7724 0.7606 0.7415 0.7248 0.7174 0.6829 0.67 0.6679 0.6613 0.6439 LOX SPARC COL1A1 BGN COL1A2 INHBA LOXL2 UPA THY1 GJB2 SFRP2 0.7433 0.7065 0.695 0.62 0.604 0.5981 0.5865 0.5672 0.5664 0.5599 MMP2 COL1A2 SPARC THBS1 CDH11 ITGA5 TAGLN PDGFRA VIM CALD1 NRP2 0.7886 0.7229 0.7172 0.7019 0.6969 0.6663 0.6662 0.6556 0.6356 0.6188 MYLK TAGLN MYH11 CALD1 IGFBP5 IGFBP7 CDH11 TLN1 CRYAB NRP2 PDGFRA 0.7671 0.7329 0.6846 0.6532 0.6456 0.6347 0.6335 0.6075 0.6057 0.5934 NRP2 TAGLN SPARC TIMP2 BGN THBS1 CDH11 COL1A2 VIM PDGFC CALD1 0.6954 0.6845 0.668 0.6663 0.6638 0.6615 0.6601 0.6532 0.6436 0.6417 PAI1 THBS1 CTGF ITGA5 DUSP1 CYR61 CTSL INHBA SPARC TIMP1 COL1A2 0.6802 0.6763 0.671 0.6545 0.6477 0.6296 0.6138 0.6079 0.6019 0.59 PDGFC TIMP2 ANTXR1 SPARC CDH11 CALD1 BGN COL1A2 TAGLN IGFBP7 SFRP4 0.707 0.6992 0.6961 0.6845 0.6822 0.6788 0.6684 0.654 0.6538 0.6487 SFRP2 BGN TGFB3 COL1A1 FAP SPARC CTHRC1 TIMP2 CTGF CXCL12 COL1A2 0.811 0.7782 0.7263 0.7189 0.6994 0.699 0.6864 0.6688 0.6649 0.6536 SFRP4 ANTXR1 CDH11 TIMP2 BGN IGFBP7 PDGFC SFRP2 SPARC FAP CTHRC1 0.7154 0.6734 0.6702 0.6662 0.6558 0.6487 0.6397 0.6291 0.6256 0.6103 SPARC COL1A1 BGN COL1A2 TIMP2 CDH11 INHBA IGFBP7 TAGLN LOXL2 THY1 0.8713 0.8711 0.8549 0.7967 0.7831 0.774 0.7715 0.7667 0.7606 0.7512 TAGLN IGFBP7 IGFBP5 MYLK SPARC CALD1 CDH11 TIMP2 NRP2 HSPG2 MYH11 0.8225 0.7829 0.7671 0.7667 0.7452 0.7338 0.7004 0.6954 0.6857 0.6706 TGFB3 BGN SFRP2 COL1A1 TIMP2 ANTXR1 SPARC FAP WISP1 THY1 DLC1 0.8147 0.7782 0.7491 0.7331 0.7119 0.7095 0.7001 0.6652 0.6538 0.6465 THBS1 CTGF COL1A2 SPARC MMP2 ITGA5 PAI1 VIM INHBA NRP2 CDH11 0.7694 0.7409 0.7207 0.7172 0.7058 0.6802 0.6723 0.6685 0.6638 0.6635 THY1 ANTXR1 SPARC IGFBP7 HSPG2 BGN TIMP2 COL1A1 ADAMTS12 TGFB3 TAGLN 0.7696 0.7512 0.7428 0.7425 0.7365 0.7327 0.7241 0.6665 0.6538 0.6334 TIMP1 SPARC BGN THBS1 COL1A2 CDH11 CTSL IGFBP5 ITGA5 NRP2 NRP1 0.7068 0.6713 0.6534 0.6518 0.6452 0.6448 0.6403 0.6374 0.6172 0.6172 TIMP2 BGN ANTXR1 COL1A1 SPARC CDH11 HSPG2 FAP TGFB3 THY1 WISP1 0.8446 0.8358 0.8071 0.7967 0.7629 0.7455 0.7364 0.7331 0.7327 0.7263 TIMP3 CTHRC1 BGN FAP TIMP2 ANTXR1 INHBA COL1A1 LOXL2 PDGFC SFRP2 0.7078 0.7053 0.7027 0.6967 0.6644 0.6364 0.6306 0.6125 0.6098 0.6064 TK1 MAD2L1 SURV H2AFZ RRM2 ENO1 KI_67 CDC2 NME1 TGFBR2 NEK2 0.6019 0.5979 0.5314 0.5176 0.5122 0.5071 0.4933 0.4871 −0.481 0.4805 TLN1 VIM THBS1 TAGLN MYLK NRP2 IGFBP5 CALD1 CTGF COL1A2 DLC1 0.6549 0.64 0.6343 0.6335 0.6271 0.6221 0.6219 0.616 0.6146 0.5982 TMEPAI NKD TGFBI ATP5E TS REG4 ATP5A1 VEGFB PTCH STMY3 IGFBP7 0.5264 0.5239 0.4626 −0.4341 −0.4322 −0.4302 0.4282 0.4207 0.4173 0.4093 TMSB10 ENO1 ANXA2 PKR2 TLN1 UBE2M RHOC C20ORF126 SBA2 TP P21 0.6212 0.5169 0.5159 0.478 0.4447 0.4332 −0.4296 0.427 0.422 0.4205 TOP2A CDC6 CENPF BRCA1 NME1 SURV KIFC1 MYBL2 BUB1 AURKB C20_ORF1 0.6143 0.4655 0.4571 0.4544 0.4375 0.429 0.4194 0.4151 0.3996 0.3958 TP CTSL GBP2 CD18 SOD2 DPYD CIAP2 CTSB UPA CD68 TIMP1 0.6975 0.6434 0.6321 0.6191 0.598 0.5636 0.5461 0.5406 0.538 0.5303 TS ATP5A1 CDC20 AURKB DHFR PKR2 TMEPAI ATP5E RAD54L REG4 LMNB1 0.5525 0.4872 0.4854 0.4849 0.4591 −0.4341 −0.4303 0.4291 0.4205 0.417 UBE2C CSEL1 STK15 MYBL2 C20_ORF1 E2F1 MCM2 CDC2 EREG C20ORF126 ATP5E 0.6581 0.6551 0.5006 0.4835 0.4385 0.411 0.4031 0.3927 0.3874 0.378 UNC5B THY1 BGN ANTXR1 TGFB3 TIMP2 SPARC IGFBP7 HSPG2 COL1A1 ADAMTS12 0.5755 0.5594 0.5589 0.5417 0.5283 0.5236 0.5191 0.5055 0.4997 0.4958 UPA CTSL INHBA THBS1 ITGA5 COL1A2 SPARC CTHRC1 BGN COL1A1 TIMP1 0.6558 0.6399 0.639 0.6357 0.629 0.6223 0.6173 0.6109 0.6014 0.6013 VCL TAGLN SPARC TIMP2 TLN1 NRP2 CDH11 COL1A2 HSPG2 THBS1 IGFBP7 0.6246 0.6024 0.5972 0.581 0.5726 0.5583 0.5515 0.5512 0.5494 0.544 VCP CAPG BAD NOTCH1 GSK3B H2AFZ MAD2L1 TUFM KI_67 IGFBP7 RCC1 0.5823 0.5384 0.4991 0.4936 0.4724 0.4564 0.437 0.4343 0.4286 0.4176 VDAC2 HDAC1 SLC25A3 HNRPAB PKR2 TS SEMA4B CHK1 CKS2 CDC2 CCNB1 0.5109 0.4867 0.4316 0.4196 0.3748 0.3683 0.364 0.3575 0.353 0.3506 VEGFB IGFBP7 TAGLN THY1 PTP4A3_V2 IGFBP5 PTCH CDH11 BAD CAPG TMEPAI 0.6369 0.5024 0.4866 0.478 0.4614 0.4445 0.4398 0.4357 0.4327 0.4282 VEGF VEGF_ALTSPLICE1 VEGF_ALTSPLICE2 HSPA1B EFNA1 CLAUDIN_4 STC1 AXIN1 TERC MGAT5 CDCA7_V2 0.6894 0.5931 0.3855 0.358 0.3175 0.3044 0.2826 0.2711 0.258 0.2354 VEGF_ALTSPLICE1 VEGF_ALTSPLICE2 VEGF CMYC THBS1 EFNA1 NEDD8 CLIC1 NOTCH1 CDCA7_V2 TMSB10 0.7502 0.6894 0.3686 0.3599 0.3577 −0.3552 0.3464 0.3459 0.3414 0.3389 VEGF_ALTSPLICE2 VEGF_ALTSPLICE1 VEGF ITGB1 THBS1 CTGF TP53BP2 CLIC1 MGAT5 EFNA1 HIF1A 0.7502 0.5931 0.4269 0.4235 0.407 0.402 0.3923 0.3788 0.3739 0.3704 VIM COL1A2 SPARC CTGF THBS1 BGN MMP2 TLN1 NRP2 TAGLN CDH11 0.6897 0.6773 0.6747 0.6723 0.6625 0.6556 0.6549 0.6532 0.6463 0.6376 WISP1 BGN COL1A1 TIMP2 FAP SPARC ANTXR1 CTHRC1 TGFB3 INHBA SFRP2 0.7682 0.7442 0.7263 0.7147 0.694 0.6679 0.666 0.6652 0.6599 0.6292 WNT2 THY1 ANTXR1 BGN SFRP4 CDH11 TIMP2 IGFBP7 SPARC COL1A1 ADAMTS12 0.5223 0.5044 0.4897 0.4823 0.4823 0.4699 0.4484 0.4412 0.4381 0.4268

TABLE 5 Results of Identification of Genes Through Gene Module/Clique Analysis of Validated Gene Biomarkers Validated Gene Co-expressed genes (Pearson co-expression coefficient) AXIN2 NKD (0.72) CDX2 CRIPTO EPHB2 PTCH ROCK2 CAD17 (0.66) [TDGF1] (0.56) (0.50) (0.49) (0.45) (0.64) CDCA7 MGAT5 PTP4A3 (0.45) (0.41) (0.40) BGN COL1A1 SPARC TIMP2 FAP ANTXR1 TGFB3 SFRP2 (0.90) (0.87) (0.84) (0.82) (0.82) (0.81) (0.81) INHBA WISP1 CTHRC1 LOXL2 COL1A2 THY1 CDH11 (0.79) (0.77) (0.77) (0.74) (0.74) (0.74) (0.73) TIMP3 ADAMTS12 LOX CTGF CXCL12 PDGFC (0.71) (0.70) (0.70) (0.69) (0.68) (0.68) cMYC HSPE1 NME1 TERC EREG AREG NOTCH1 MYBL2 (0.55) (0.49) (0.48) (0.47) (.046) (0.46) (0.45) CSEL1 C_SRC SNRPF E2F1 (0.44) ATP5E UMPS PRDX4 (0.45) (0.44) (0.44) (0.44) (0.43) (0.40) CDX2 MAD2L1 (0.40) (0.40) EFNB2 LAMC2 KLF5 SPRY2 (0.46) (0.43) (0.42) FAP BGN COL1A1 CTHRC1 TIMP2 INHBA ANTXR1 SFRP2 (0.82) (0.78) (0.77) (0.74) (0.73) (0.73) (0.72) WISP1 TIMP3 TGFB3 SPARC LOXL2 SFRP4 COL1A2 (0.72) (0.70) (0.70) (0.67) (0.64) (0.63) (0.62) CYP1B1 CDH11 CTSB PDGFC CXCL12 MCP1 (0.62) (0.61) (0.61) (0.59) (0.59) (0.59) GADD45B DUSP1 PAI1 CTGF CYR61 INHBA BGN SPARC (0.59) (0.58) (0.58) (0.53) (0.56) (0.52) (0.51) UPA THBS1 PLK3 TIMP1 SFRP2 CYP1B1 VIM (0.50) (0.50) (0.49) (0.49) (0.48) (0.47) (0.47) LOX TAGLN CXCL12 WISP1 TGFB3 STC1 (0.46) (0.46) (0.46) (0.46) (0.45) (0.45) HSPE1 CCNB1 CMYC NME1 SNRPF HNRPAB RRM2 RBX1 (0.57) (0.55) (0.53) (0.52) (0.50) (0.48) (0.48) ODC1 MAD2L1 MSH2 AREG HSPA8 CD44E THY1 (0.47) (0.46) (0.41) (0.41) (0.41) (0.40) (0.40) INHBA BGN SPARC CTHRC1 FAP COL1A1 CTGF COL1A2 (0.79) (0.77) (0.74) (0.73) (0.72) (0.71) (0.72) CDH11 THBS1 LOXL2 TIMP2 WISP1 SFRP2 UPA (0.67) (0.67) (0.66) (0.66) (0.66) (0.64) (0.64) TIMP3 ANTXR1 CYR61 PAI1 PDGFC ADAMTS12 (0.64) (0.64) (0.63) (0.61) (0.61) (0.61) Ki67 CDC2 MAD2L1 H2AFZ BUB1 CDC20 SURV TK1 (0.69) (0.60) (0.58) (0.54) (0.52) (0.51) (0.51) NEK2 LMNB1 RRM2 SNRPF CCNB1 KIFC1 RAD54L (0.51) (0.50) (0.48) (0.47) (0.47) (0.46) (0.46) ESPL1 PCNA KIF22 CDC25C VCP MCM3 (0.46) (0.45) (0.44) (0.44) (0.43) (0.43) MAD2L1 H2AFZ CDC2 SNRPF TK1 KI_67 SURV CCNB1 (0.64) (0.62) (0.61) (0.60) (0.60) (0.58) (0.57) RRM2 NEK2 BUB1 NME1 MCM3 BAD HSPE1 (0.56) (0.55) (0.53) (0.51) (0.49) (0.47) (0.46) VCP TGFBR2 KRT8 PCNA CDC20 RCC1 (0.46) (0.45) (0.44) (0.44) (0.44) (0.43) MYBL2 C20_ORF1 E2F1 UBE2C STK15 CSEL1 CMYC ATP5E (0.56) (0.55) (0.50) (0.46) (0.46) (0.52) (0.42) TOP2A CDCA7 (0.42) (0.41) RUNX1 CDH11 TIMP2 PDGFC ANTXR1 BGN CALD1 FZD1 (0.57) (0.55) (0.54) (0.53) (0.52) (0.52) (0.51) SPARC IGFBP7 INHBA NRP2 AKT3 SFRP4 COL1A2 (0.50) (0.50) (0.50) (0.49) (0.49) (0.49) (0.49) CTHRC1 FAP WISP1 TGFB3 TAGLN TIMP3 (0.48) (0.48) (0.48) (0.47) (0.47) (0.47)

TABLE 6 Gene Cliques Identified for Validated Genes Seeding Spearman Gene AffyProbeID Weight Cliqued Gene Cutoff FAP 9441 19 FAP 0.5 FAP 13949 4 DKFZp434K191 0.5 FAP 13949 4 POM121L1 0.5 FAP 13949 4 LOC646074 0.5 FAP 13949 4 LOC100133536 0.5 FAP 13949 4 LOC651452 0.5 FAP 13949 4 LOC729915 0.5 FAP 13949 4 DKFZP434P211 0.5 FAP 13949 4 LOC728093 0.5 FAP 7405 3 CALCR 0.5 FAP 9568 3 TPSAB1 0.5 FAP 10493 3 TLX2 0.5 FAP 15164 3 0.5 FAP 15197 3 NUDT7 0.5 FAP 16536 3 IGHA1 0.5 FAP 20381 3 LRRC3 0.5 FAP 4496 2 RDX 0.5 FAP 4839 2 SPI1 0.5 FAP 6242 2 UMOD 0.5 FAP 9590 2 RDH5 0.5 FAP 15576 2 COMT 0.5 FAP 16692 2 0.5 FAP 18423 2 LYVE1 0.5 FAP 6479 1 LPHN2 0.5 FAP 10429 1 HLA-DRA 0.5 FAP 16097 1 STK38 0.5 FAP 19846 1 SERGEF 0.5 FAP 20724 1 OMP 0.5 HSPE1 4660 569 HSPE1 0.5 HSPE1 15676 338 YME1L1 0.5 HSPE1 746 302 CTBP2 0.5 HSPE1 1358 265 NET1 0.5 HSPE1 1697 174 AASDHPPT 0.5 HSPE1 17578 146 C11orf10 0.5 HSPE1 18720 139 CHMP5 0.5 HSPE1 12550 138 SP3 0.5 HSPE1 10354 133 PDCD10 0.5 HSPE1 879 132 YME1L1 0.5 HSPE1 8855 123 MED21 0.5 HSPE1 1181 102 CNIH 0.5 HSPE1 17414 98 MRPL13 0.5 HSPE1 471 97 HMGN1 0.5 HSPE1 17704 96 MRPL22 0.5 HSPE1 13816 95 SHMT2 0.5 HSPE1 10513 85 SUMO1 0.5 HSPE1 22252 81 0.5 HSPE1 8637 79 CLNS1A 0.5 HSPE1 9151 74 CETN3 0.5 HSPE1 92 73 SMNDC1 0.5 HSPE1 437 72 RPLP2 0.5 HSPE1 3713 63 PPID 0.5 HSPE1 3111 62 TTC35 0.5 HSPE1 20668 60 UGT1A9 0.5 HSPE1 20668 60 UGT1A6 0.5 HSPE1 20668 60 UGT1A8 0.5 HSPE1 11526 54 PDS5A 0.5 HSPE1 108 53 TMED2 0.5 HSPE1 12094 52 NUP160 0.5 HSPE1 8110 48 PDIA3 0.5 HSPE1 17336 48 MAP2K1IP1 0.5 HSPE1 11983 47 WDFY3 0.5 HSPE1 17192 45 SPG21 0.5 HSPE1 495 39 PPIB 0.5 HSPE1 17591 39 NDUFB4 0.5 HSPE1 17591 39 LOC727762 0.5 HSPE1 9287 37 PRKAA1 0.5 HSPE1 31 35 RPL11 0.5 HSPE1 19126 30 RPL36 0.5 HSPE1 166 29 YWHAZ 0.5 HSPE1 8914 29 MSH2 0.5 HSPE1 1060 28 PSMA3 0.5 HSPE1 21589 26 LOC441533 0.5 HSPE1 1241 25 RANBP2 0.5 HSPE1 7592 24 ITGB6 0.5 HSPE1 20791 24 TBL1XR1 0.5 HSPE1 2992 23 MRPL19 0.5 HSPE1 4412 23 MSLN 0.5 HSPE1 801 22 hCG_1781062 0.5 HSPE1 801 22 SRP9 0.5 HSPE1 17967 22 FAM29A 0.5 HSPE1 8189 20 PRKDC 0.5 HSPE1 15646 18 SEC11A 0.5 HSPE1 120 16 RPS3A 0.5 HSPE1 120 16 LOC439992 0.5 HSPE1 112 14 RPS25 0.5 HSPE1 395 14 ZNF313 0.5 HSPE1 8347 14 CANX 0.5 HSPE1 11315 14 TUT1 0.5 HSPE1 11315 14 EEF1G 0.5 HSPE1 8766 13 NAB1 0.5 HSPE1 18447 13 SHQ1 0.5 HSPE1 1170 12 IFNGR2 0.5 HSPE1 19696 12 CLDN16 0.5 HSPE1 17528 11 MCTS1 0.5 HSPE1 38 10 RPS27A 0.5 HSPE1 38 10 UBC 0.5 HSPE1 38 10 UBB 0.5 HSPE1 309 10 RPS15A 0.5 HSPE1 10762 10 EEF1G 0.5 HSPE1 10762 10 TUT1 0.5 HSPE1 4819 9 HNRNPA2B1 0.5 HSPE1 10894 9 RPS17 0.5 HSPE1 20002 9 CBLC 0.5 HSPE1 4294 8 FEN1 0.5 HSPE1 417 7 SSR1 0.5 HSPE1 3271 6 HMGB3 0.5 HSPE1 7814 6 C7orf28A 0.5 HSPE1 7814 6 C7orf28B 0.5 HSPE1 11918 6 WEE1 0.5 HSPE1 3474 5 CSTF3 0.5 HSPE1 19605 5 TMCO3 0.5 HSPE1 231 4 DYNLL1 0.5 HSPE1 296 4 MAT2A 0.5 HSPE1 863 4 ARHGEF12 0.5 HSPE1 4185 4 TRA2A 0.5 HSPE1 18483 4 LSM8 0.5 HSPE1 21253 3 ADCK2 0.5 HSPE1 926 2 LOC100130862 0.5 HSPE1 926 2 TRAM1 0.5 HSPE1 4761 2 SLC16A4 0.5 HSPE1 19884 2 NUP62CL 0.5 HSPE1 47 1 RPL34 0.5 HSPE1 1155 1 INSIG1 0.5 HSPE1 2415 1 DDIT4 0.5 HSPE1 3473 1 ARG2 0.5 HSPE1 11997 1 RCOR1 0.5 HSPE1 16678 1 0.5 INHBA 9981 4 INHBA 0.5 INHBA 1386 2 SRGN 0.5 INHBA 21897 2 COL11A1 0.5 INHBA 1320 1 AEBP1 0.5 INHBA 5099 1 ANGPT2 0.5 INHBA 5939 1 TCL6 0.5 INHBA 5939 1 TCL1B 0.5 INHBA 9047 1 CD36 0.5 MAD2L1 2889 5 MAD2L1 0.5 MAD2L1 4862 3 SRP19 0.5 MAD2L1 3962 2 NUPL1 0.5 MAD2L1 4484 2 ORC5L 0.5 MAD2L1 12103 2 PAPOLA 0.5 MAD2L1 2863 1 ITGB1BP1 0.5 KI67 11408 15 KI67 0.5 KI67 11409 15 KI67 0.5 KI67 11406 14 KI67 0.5 KI67 986 13 BUB3 0.5 KI67 9460 10 BUB3 0.5 KI67 8882 9 DBI 0.5 KI67 320 8 XRCC6 0.5 KI67 1717 8 PTBP1 0.5 KI67 7951 8 XPNPEP1 0.5 KI67 8574 7 GLRX3 0.5 KI67 11181 7 SFRS1 0.5 KI67 11407 7 KI67 0.5 KI67 17827 7 BXDC5 0.5 KI67 100 5 KARS 0.5 KI67 2694 5 CFDP1 0.5 KI67 12471 5 DNAJC9 0.5 KI67 484 4 SSRP1 0.5 KI67 791 4 TARS 0.5 KI67 1005 4 RRM1 0.5 KI67 1622 4 BIRC5 0.5 KI67 17411 4 MRPS16 0.5 KI67 424 3 HDGF 0.5 KI67 1083 3 MCM3 0.5 KI67 2427 3 SFRS3 0.5 KI67 2738 3 RFC5 0.5 KI67 3271 3 HMGB3 0.5 KI67 8303 3 HMGB2 0.5 KI67 9311 3 UCK2 0.5 KI67 12916 3 UBE2I 0.5 KI67 17225 3 NDUFA10 0.5 KI67 17225 3 LOC732160 0.5 KI67 17720 3 KIF4A 0.5 KI67 19014 3 ERCC6L 0.5 KI67 1298 2 SNRPA 0.5 KI67 1302 2 NCAPD2 0.5 KI67 1424 2 PSRC1 0.5 KI67 3779 2 CDK2 0.5 KI67 6025 2 SNHG3-RCC1 0.5 KI67 6025 2 RCC1 0.5 KI67 8746 2 HARS2 0.5 KI67 17338 2 DCXR 0.5 KI67 17441 2 ARHGAP17 0.5 KI67 17907 2 CEP55 0.5 KI67 18151 2 CWF19L1 0.5 KI67 899 1 CUL3 0.5 KI67 1381 1 CDC25B 0.5 KI67 3033 1 MED12 0.5 KI67 8957 1 AURKB 0.5 KI67 9538 1 TAF5 0.5 KI67 11401 1 PTBP1 0.5 KI67 13174 1 NGDN 0.5 KI67 18311 1 PAPD1 0.5 KI67 19342 1 NUSAP1 0.5 RUNX1 10265 38 RUNX1 0.6 RUNX1 10621 21 RUNX1 0.6 RUNX1 10624 11 RUNX1 0.6 RUNX1 16111 11 0.6 RUNX1 15586 10 0.6 RUNX1 7955 9 GABRD 0.6 RUNX1 13947 9 TPSD1 0.6 RUNX1 16761 9 0.6 RUNX1 6124 8 INS 0.6 RUNX1 9341 8 KLK2 0.6 RUNX1 15333 8 F12 0.6 RUNX1 15717 8 SEC14L3 0.6 RUNX1 19749 8 JPH2 0.6 RUNX1 2021 7 CSH1 0.6 RUNX1 2021 7 CSH2 0.6 RUNX1 2021 7 GH1 0.6 RUNX1 2021 7 FCHO2 0.6 RUNX1 14776 7 APPBP2 0.6 RUNX1 16935 7 0.6 RUNX1 13242 6 PNPLA2 0.6 RUNX1 17026 6 SIX5 0.6 RUNX1 7844 5 CSH1 0.6 RUNX1 7844 5 GH1 0.6 RUNX1 7844 5 CSH2 0.6 RUNX1 7907 5 GRAP2 0.6 RUNX1 10097 5 SGCA 0.6 RUNX1 4397 4 PCSK2 0.6 RUNX1 8058 4 KCNA10 0.6 RUNX1 9957 4 CLEC4M 0.6 RUNX1 14240 4 DOT1L 0.6 RUNX1 20209 4 ACOXL 0.6 RUNX1 7167 3 CDY2A 0.6 RUNX1 7167 3 CDY1 0.6 RUNX1 7167 3 CDY2B 0.6 RUNX1 7167 3 CDY1B 0.6 RUNX1 7985 3 LMX1B 0.6 RUNX1 8006 3 OR2J2 0.6 RUNX1 8070 3 HIST3H3 0.6 RUNX1 11037 3 IGHG1 0.6 RUNX1 11044 3 IGHG1 0.6 RUNX1 11044 3 LOC100133862 0.6 RUNX1 11044 3 IGHA1 0.6 RUNX1 13294 3 NKG7 0.6 RUNX1 14153 3 IGKV4-1 0.6 RUNX1 14518 3 0.6 RUNX1 16170 3 0.6 RUNX1 16401 3 KRT84 0.6 RUNX1 19748 3 TXNDC3 0.6 RUNX1 19870 3 GUCY1B2 0.6 RUNX1 6932 2 LECT2 0.6 RUNX1 9485 2 SOCS1 0.6 RUNX1 10358 2 ID2B 0.6 RUNX1 11241 2 PVRL1 0.6 RUNX1 11266 2 PCDHGA11 0.6 RUNX1 14875 2 0.6 RUNX1 15862 2 IGHM 0.6 RUNX1 16087 2 FAM48A 0.6 RUNX1 16200 2 LOC390561 0.6 RUNX1 16200 2 LOC730909 0.6 RUNX1 16568 2 RASAL2 0.6 RUNX1 16937 2 0.6 RUNX1 18968 2 ZNF3 0.6 RUNX1 20168 2 TP73 0.6 RUNX1 21214 2 PKP1 0.6 RUNX1 3849 1 GOLIM4 0.6 RUNX1 5706 1 ZNF747 0.6 RUNX1 7412 1 SRY 0.6 RUNX1 7412 1 LOC100130809 0.6 RUNX1 13490 1 OPCML 0.6 RUNX1 13739 1 SMARCA4 0.6 RUNX1 13844 1 ORM1 0.6 RUNX1 13844 1 ORM2 0.6 RUNX1 15714 1 PCDHGA3 0.6 RUNX1 19633 1 ZBBX 0.6 RUNX1 20562 1 GFRA4 0.6 RUNX1 21537 1 SCAND2 0.6 RUNX1 21554 1 LOC100132923 0.6

TABLE 7 Datasets used for gene clique analysis of prognostic and predictive genes GEO Accession Number of Number Tumor Samples GSE1323 6 GSE2138 20 GSE2509 6 GSE2742 27 GSE5364 9

TABLE 8 Association of gene expression and risk of recurrence in surgery alone patients from the QUASAR study HR LR Gene N HR 95% CI p-value Axin_2 711 1.13 (1.00, 1.28) 0.046 BIK 711 0.61 (0.47, 0.80) 0.0002 EFNB2 711 1.71 (1.40, 2.08) 3.9E−07 HSPE1 711 0.75 (0.56, 1.00) 0.054 MAD2L1 711 0.66 (0.52, 0.84) 0.0006 RUNX1 711 1.76 (1.37, 2.26) 7.6E−06 BGN 711 1.31 (1.11, 1.55) 0.001 FAP 711 1.48 (1.16, 1.87) 0.002 INHBA 711 1.35 (1.13, 1.62) 0.001 Ki_67 711 0.63 (0.47, 0.83) 0.001 MYBL2 711 0.98 (0.74, 1.28) 0.86 cMYC 711 0.93 (0.79, 1.11) 0.44 GADD45B 711 1.17 (0.95, 1.44) 0.14

TABLE 9 Results of the meta analysis and stratified Cox models META Stratified analysis Cox Model Gene HR 95% CI HR 95% CI Axin_2 0.99 (0.89, 1.09) 1.00 (0.95, 1.05) BIK 0.75 (0.64, 0.88) 0.74 (0.65, 0.83) EFNB2 1.37 (1.23, 1.54) 1.38 (1.26, 1.52) HSPE1 0.77 (0.67, 0.88) 0.80 (0.73, 0.89) MAD2L1 0.67 (0.61, 0.75) 0.67 (0.61, 0.75) RUNX1 1.38 (1.14, 1.68) 1.38 (1.23, 1.55) BGN 1.29 (1.19, 1.39) 1.28 (1.19, 1.38) INHBA 1.29 (1.19, 1.39) 1.29 (1.19, 1.39) FAP 1.23 (1.15, 1.31) 1.24 (1.15, 1.34) Ki_67 0.74 (0.69, 0.81) 0.75 (0.68, 0.84) cMYC 0.84 (0.78, 0.90) 0.83 (0.76, 0.90) MYBL2 0.86 (0.79, 0.93) 0.86 (0.80, 0.94) GADD45B 1.20 (1.12, 1.29) 1.23 (1.11, 1.37)

Claims

1. A method for obtaining a Recurrence Score (RS) result for a patient with colorectal cancer, comprising:

measuring levels of RNA transcripts of a set of genes consisting of BGN, FAP, INHBA, MYBL2, Ki-67, cMYC, and GADD45B, and at least one reference gene in a tumor sample obtained from the patient;
normalizing levels of the RNA transcripts of BGN, FAP, INHBA, MYBL2, Ki-67, cMYC, and GADD45B against the levels of the RNA transcripts of at the least one reference gene to provide normalized levels of the RNA transcripts of BGN, FAP, INHBA, MYBL2, Ki-67, cMYC, and GADD45B;
assigning the normalized levels to gene subsets comprising a stromal group and a cell cycle group and a cell signaling group, wherein the stromal group comprises FAP, BGN, and INHBA, and the cell cycle group comprises Ki-67, cMYC, and MYBL2 and the cell signaling group comprises GADD45B;
wherein the level of normalized RNA transcripts from the stromal group selected from BGN, FAP, and INHBA is measured to obtain a stromal group score, the level of normalized RNA transcripts from the cell cycle group selected from MYBL2, Ki-67, and cMYC is measured to obtain a cell cycle group score, and the level of the normalized RNA transcript of GADD45B is measured to obtain a cell signaling group score, wherein the stromal group score, cell cycle group score, and cell signaling group score equal the sum of the normalized RNA transcript levels for each gene of the group divided by the number of genes in the group;
weighting the stromal group score by +0.15, weighting the cell cycle group score by −0.3 and weighting the cell signaling group score by +0.15;
calculating a Recurrence Score (RS) result for the patient using the weighted gene group scores; and
generating a report comprising the RS result.

2. The method of claim 1, wherein the normalized levels of the RNA transcripts are further calculated as a ratio of the normalized levels to tumor region, wherein the tumor region is tumor-associated stroma unit area or tumor epithelia unit area.

3. The method of claim 1, further comprising:

measuring a surface area of tumor-associated stroma in the tumor sample and calculating a Stromal Risk Score based on the surface area of the tumor-associated stroma,
wherein increased Stromal Risk Score is positively correlated to increased risk of recurrence of cancer for said patient; and
wherein the report further comprises the Stromal Risk Score.

4. The method of claim 1, wherein the tumor sample is obtained from a biopsy.

5. The method of claim 1, wherein the tumor sample is fresh or frozen.

6. The method of claim 1, wherein the levels of the RNA transcripts are measured by reverse transcription polymerase chain reaction (RT-PCR).

7. The method of claim 1, further comprising scaling the RS result on a scale of 0 to 100, wherein the scaled RS result=0 if 44×(RS+0.82)<0, the RS=100 if 44×(RS+0.82)>100, and wherein the scaled RS result=44×(RS+0.82) when 44×(RS+0.82) has a value ≥0 and ≤100.

8. The method of claim 1, further comprising determining a recurrence risk group tier for the patient based on the patient's scaled RS result in comparison to a set of at least three previously defined recurrence risk group tiers.

9. The method of claim 8, wherein the recurrence risk group tiers comprise a low risk group tier if the patient's scaled RS result is <30, an intermediate risk group tier if the patient's scaled RS result is ≥30 to <41, and a high risk group tier if the patient's scaled RS result is ≥41.

10. The method of claim 1, wherein the RS result for the patient is calculated from the sum of the weighted stromal group score, the weighted cell cycle group score, and the weighted cell signaling group score.

11. The method of claim 1, wherein the tumor sample is a paraffin embedded and fixed sample.

12. The method of claim 1, wherein the at least one reference gene comprises one or more of ATP5E, PGK1, GPX1, UBB, and VDAC2.

13. The method of claim 1, wherein the at least one reference gene consists of one to five genes.

14. A method for obtaining a Recurrence Score (RS) result for a patient with colorectal cancer, comprising:

extracting RNA from a tumor sample obtained from the patient;
reverse transcribing RNA transcripts of a set of genes consisting of BGN, FAP, INHBA, MYBL2, Ki-67, cMYC, and GADD45B, and at least one reference gene to produce cDNAs;
amplifying the cDNAs to produce amplicons of the RNA transcripts of the genes;
assaying levels of the amplicons;
normalizing the levels of the amplicons of BGN, FAP, INHBA, MYBL2, Ki-67, cMYC, and GADD45B against the level of the amplicon of the at least one reference RNA transcript in said tumor sample to provide normalized amplicon levels of the BGN, FAP, INHBA, MYBL2, Ki-67, cMYC, and GADD45B RNA transcripts;
assigning the normalized amplicon levels to gene subsets comprising a stromal group and a cell cycle group and a cell signaling group to obtain a stromal group score and a cell cycle group score and a cell signaling group score, wherein the stromal group score equals the sum of the normalized amplicon levels of FAP, BGN, and INHBA divided by three, the cell cycle group score equals the sum of the normalized amplicon levels of Ki-67, cMYC, and MYBL2 divided by three, and the cell signaling group score equals the normalized amplicon level of GADD45B;
weighting the stromal group score by +0.15, weighting the cell cycle group score by −0.3, and weighting the cell signaling group score by +0.15;
calculating a recurrence score (RS) result for the patient from the sum of the weighted stromal group score, the weighted cell cycle group score, and the weighted cell signaling group score; and
generating a report comprising the RS result.

15. The method of claim 14, wherein the tumor sample is fresh, frozen.

16. The method of claim 14, further comprising:

measuring a surface area of tumor-associated stroma in the tumor sample and calculating a Stromal Risk Score based on the surface area of the tumor-associated stroma,
wherein increased Stromal Risk Score is positively correlated to increased risk of recurrence of cancer for said patient; and
wherein the report further comprises the Stromal Risk Score.

17. The method of claim 14, wherein the tumor sample is obtained from a biopsy.

18. The method of claim 14, further comprising scaling the RS result on a scale of 0 to 100, wherein the scaled RS result =0 if 44×(RS+0.82)<0, the RS=100 if 44×(RS+0.82)>100, and wherein the scaled RS result=44×(RS+0.82) when 44×(RS+0.82) has a value ≥0 and ≤100.

19. The method of claim 14, further comprising determining a recurrence risk group tier for the patient based on the patient's scaled RS in comparison to a set of at least three previously defined recurrence risk group tiers.

20. The method of claim 19, wherein the recurrence risk group tiers comprise a low risk group tier if the patient's scaled RS is <30, an intermediate risk group tier if the patient's scaled RS is ≥30 to <41, and a high risk group tier if the patient's scaled RS is ≥41.

21. The method of claim 14, wherein the tumor sample is a paraffin embedded and fixed sample.

22. The method of claim 14, wherein the at least one reference gene comprises one or more of ATP5E, PGK1, GPX1, UBB, and VDAC2.

23. The method of claim 14, wherein the at least one reference gene consists of one to five genes.

24. A method of analyzing the expression of RNA transcripts of genes in a colorectal cancer patient, comprising:

extracting RNA from a tumor sample obtained from the patient;
reverse transcribing RNA transcripts of a set of genes consisting of BGN, FAP, INHBA, MYBL2, Ki-67, cMYC, and GADD45B, and at least one reference gene, in the tumor sample to produce cDNAs, wherein a reference gene is a gene that does not exhibit a significantly different RNA expression level in in cancerous colorectal tissue compared to non-cancerous colorectal tissue; and
amplifying the cDNAs to produce amplicons of the RNA transcripts of the genes for use in determining expression levels of the RNA transcripts.

25. The method of claim 24, wherein the at least one reference gene comprises one or more of ATP5E, PGK1, GPX1, UBB, and VDAC2.

Referenced Cited
U.S. Patent Documents
6692916 February 17, 2004 Bevilacqua et al.
6960439 November 1, 2005 Bevilacqua et al.
6964850 November 15, 2005 Bevilacqua et al.
7695913 April 13, 2010 Cowens et al.
7767391 August 3, 2010 Scott et al.
8008003 August 30, 2011 Baker et al.
8026060 September 27, 2011 Cowens et al.
8029995 October 4, 2011 Cowens et al.
8067178 November 29, 2011 Baker et al.
8148076 April 3, 2012 Baker et al.
8153378 April 10, 2012 Cowens et al.
8153379 April 10, 2012 Cowens et al.
8153380 April 10, 2012 Cowens et al.
20010044414 November 22, 2001 Clark et al.
20020150922 October 17, 2002 Stolk et al.
20020172987 November 21, 2002 Terstappen et al.
20030077568 April 24, 2003 Gish et al.
20030087818 May 8, 2003 Jiang et al.
20030109690 June 12, 2003 Ruben et al.
20030148314 August 7, 2003 Berger et al.
20030148410 August 7, 2003 Berger et al.
20030166064 September 4, 2003 King et al.
20030198970 October 23, 2003 Roberts
20030219760 November 27, 2003 Gordon et al.
20030225526 December 4, 2003 Golub et al.
20040053317 March 18, 2004 Glinskii
20050014165 January 20, 2005 Lee et al.
20060195269 August 31, 2006 Yeatman et al.
20060211036 September 21, 2006 Chou et al.
20070099209 May 3, 2007 Clarke et al.
20070105133 May 10, 2007 Clarke et al.
20070166704 July 19, 2007 Huang et al.
20080015448 January 17, 2008 Keely et al.
20090258795 October 15, 2009 Cowens et al.
20090298701 December 3, 2009 Baker et al.
20090305277 December 10, 2009 Baker et al.
20100291573 November 18, 2010 Cowens et al.
20110097759 April 28, 2011 Cowens et al.
20110111421 May 12, 2011 Cowens et al.
20110287958 November 24, 2011 Shak et al.
20120040842 February 16, 2012 Baker et al.
20120046186 February 23, 2012 Pelham et al.
Foreign Patent Documents
1522594 April 2005 EP
1274865 February 2007 EP
2009-523028 June 2009 JP
WO9964626 December 1999 WO
WO9964627 December 1999 WO
WO0024940 May 2000 WO
WO0141815 June 2001 WO
WO0212280 February 2002 WO
WO0212328 February 2002 WO
WO0224956 March 2002 WO
WO03050243 June 2003 WO
WO03062395 July 2003 WO
WO2004110345 December 2004 WO
WO2005000087 January 2005 WO
WO2005015236 February 2005 WO
WO2005076005 August 2005 WO
WO2005100593 October 2005 WO
2005/119260 December 2005 WO
WO2006010150 January 2006 WO
WO2006081248 August 2006 WO
WO2006110581 October 2006 WO
WO2007061876 May 2007 WO
WO2007070621 June 2007 WO
WO2007073220 June 2007 WO
2007/082099 July 2007 WO
WO 2007/082099 July 2007 WO
WO2007112330 October 2007 WO
2008/115419 September 2008 WO
Other references
  • Tsujino et al. Stromal Myofibroblasts Predict Disease Recurrence for Colorectal Cancer. Apr. 2, 2007. Clinical Cancer Research. vol. 13, pp. 2082-2090.
  • Wagner, J. Overview of biomarkers and surrogate endpoints in drug development. 2002. Disease Markers. vol. 18, pp. 41-46.
  • Frank et al. Clinical Biomarkers in Drug Discovery and Development. Jul. 2003. Nature. vol. 2, No. 7, pp. 566-580.
  • Feng et al. Research issues and strategies for genomic and proteomic biomarker discovery and validation: a statistical perspective. Sep. 2004. Pharmacogenomics. vol. 5, No. 6, pp. 709-719.
  • Golub et al. Molecular Classification of Cancer: Class Discovery and Class Prediction by Gene Expression Monitoring. Oct. 15, 1999. Science. vol. 286, p. 531-537.
  • Anjomshoaa A., et al., “Reduced Expression of a Gene Proliferation Signature is Associated with Enhanced Malignancy in Colon Cancer,” British Journal of Cancer, 2008, vol. 99, pp. 966-973.
  • Arango et al., “Gene-Expression Profiling Predicts Recurrence in Dukes' C Colorectal Cancer”, Gastroenterology, 2005, vol. 129, No. 3, pp. 874-884.
  • Augenlicht et al., “Low-Level C-Myc Amplification in Human Colonic Carcinoma Cell Lines and Tumors: A Frequent, p53-Independent Mutation Associated with Improved Outcome in a Randomized Multi-Institutional Trial,” Cancer Research, 1997, vol. 57, pp. 1769-1775.
  • Avvisato et al., “Mechanical Force Modulates Global Gene Expression and β-Catenin Signaling in Colon Cancer Cells,” Journal of Cell Science, 2007, vol. 120, pp. 2672-2682.
  • Baba et al., “Involvement of Deregulated Epiregulin Expression in Tumorigenesis In Vivo Through Activated Ki-Ras Signaling Pathway in Human Colon Cancer Cells,” Cancer Res., 2000, vol. 60, pp. 6886-6889.
  • Backus, H.H.J. et al., “Differential Expression of Cell Cycle and Apoptosis Related Proteins in Colorectal Mucosa, Primary Colon Tumors, and Liver Metastases,” J.Clin.Path., 2002, vol. 55, pp. 206-211.
  • Barrier, A. et al., “Colon Cancer Prognosis Prediction by Gene Expression Profiling,” Oncogene, 2005, vol. 24, pp. 6155-6164.
  • Barrier A. et al., “Gene Expression Profiling of Nonneoplastic Mucosa May Predict Clinical Outcome of Colon Cancer Patients”, Diseases of the Colon and Rectum, 2005, vol. 48, No. 12, pp. 2238-2248.
  • Batlle E., et al., “EphB Receptor Activity Suppresses Colorectal Cancer Progression,” Nature, 2005, vol. 435, pp. 1126-1130.
  • Bertucci et al., “Gene Expression Profiling of Primary Breast Carcinomas Using Arrays of Candidate Genes”, Human Molecular Genetics, 2000, vol. 9, pp. 2981-2991.
  • Bertucci F., et al.,“Gene Expression Profiling of Colon Cancer by DNA Microarrays and Correlation with Histoclinical Parameters,” Oncogene, 2004, vol. 23, pp. 1377-1391.
  • Bhatavdekar J.M., et al., “Coexpression of Bcl-2, c-Myc, and p53 Oncoproteins as Prognostic Discriminants in Patients with Colorectal Carcinoma,” Diseases of the Colon and Rectum, 1997, vol. 40, pp. 785-790.
  • Bhatavdekar J.M., et al., “Molecular Markers are Predictors of Recurrence and Survival in Patients with Dukes B and Dukes C Colorectal Adenocarcinoma,” Diseases of the Colon and Rectum, 2001, vol. 44, pp. 523-533.
  • Clark-Langone K.M., et al., “Biomarker Discovery for Colon Cancer Using a 761 Gene RT-PCR Assay,” BMC Genomics, 2007, vol. 8, pp. 279.
  • Collett et al., “Overexpression of p65/RelA Potentiates Curcumin-Induced Apoptosis in HCT116 Human Colon Cancer Cells,” Carcinogenesis, 2006, vol. 27, pp. 1285-1291.
  • Compton C., et al., “The Staging of Colorectal Cancer: 2004 and Beyond,” CA Cancer J. Clin., 2004, vol. 54, pp. 295-308.
  • Eschrich S., et al.,“Molecular Staging for Survival Prediction of Colorectal Cancer Patients,” J. Clin. Oncol., 2005, vol. 23, pp. 3526-3535.
  • Friederichs J., et al., “Gene Expression Profiles of Different Clinical Stages of Colorectal Carcinoma: Toward a Molecular Genetic Understanding of Tumor Progression,” Int. J. Colorectal Dis., 2005, vol. 20, pp. 391-402.
  • Glasgow S.C., et al., “Predictive and Prognostic Genetic Markers in Colorectal Cancer,” Seminars in Colon and Rectal Surgery, 2005, vol. 15, pp. 163-170.
  • Henry L.R., et al., “Clinical Implications of Fibroblast Activation Protein in Patients with Colon Cancer,” Clinical Cancer Research, 2007, vol. 13, pp. 1736-1741.
  • Iwasa S., et al., “Increased Expression of Seprase, a Membrane-type Serine Protease, is Associated with Lymph Node Metastasis in Human Colorectal Cancer,” Cancer Letters, 2005, vol. 227, pp. 229-236.
  • Jubb A.M., et al., “EphB2 is a Prognostic Factor in Colorectal Cancer,” Clinical Cancer Research, 2005, vol. 11, pp. 5181-5187.
  • Kakisako K., et al., “Prognostic Significance of c-myc mRNA Expression Assessed by Semi-quantitative RT-PCR in Patients with Colorectal Cancer,” Oncology Reports, 1998, vol. 5, pp. 441-445.
  • Kononen J. et al., “Tissue Microarrays for High-Throughput Molecular Profiling of Tumor Specimens”, Nature Medicine, 1998, vol. 4, No. 7, pp. 844-847.
  • Lee D. et al., “Epiregulin is Not Essential for Development of Intestinal Tumors but is Required for Protection from Intestinal Damage,” Mol. Cell. Biol., 2004, vol. 24, pp. 8907-8916.
  • Lee M. O. et al., “Differential Effects of Retinoic Acid on Growth and Apoptosis in Human Colon Cancer Cell Lines Associated with the Induction of Retinoic Acid Receptor Beta”, Biochemical Pharmacology, 2000, vol. 59, No. 5, pp. 485-496.
  • Liotta L.A., et al., “The Microenvironment of the Tumour-Host Interface,” Nature, 2001, vol. 411, pp. 375-379.
  • Liu W., et al., “Coexpression of Ephrin-Bs and their Receptors in Colon Carcinoma,” Cancer, 2002, vol. 94, pp. 934-939.
  • Liu W., et al., “Effects of Overexpression of Ephrin-B2 on Tumour Growth in Human Colorectal Cancer,” British Journal of Cancer, 2004, vol. 90, pp. 1620-1626.
  • Mesker et al., “The Carcinoma-Stromal Ratio of Colon Carcinoma is an Independent Factor for Survival Compared to Lymph Node Status and Tumor Stage,” Cell Oncol., 2007, vol. 29, pp. 387-398.
  • Mesker et al., “Presence of a High Amount of Stroma and Downregulation of SMAD4 Predict for Worse Survival for Stage I-II Colon Cancer Patients,” Cellular Oncology, 2009, vol. 31, pp. 169-178.
  • Modlich, O. et al., “Predictors of Primary Breast Cancers Responsiveness to Preoperative Epirubicin/Cyclophosphamide-4 Based Chemotherapy: Transition of Microarray Data Into Clinically Useful Predictive Signatures,” Journal of Translational Medicine, 2005, vol. 3, pp. 32.
  • Nakopoulou, L. et al., “Stromelysin-3 Protein Expression in Invasive Breast Cancer: Relation to Proliferation, Cell Survival and Patients' Outcome,” Modern Pathology, 2002, vol. 15, No. 11, pp. 1154-1161.
  • Nessling et al., “Candidate Genes in Breast Cancer Revealed by Microarray-Based Comparative Genomic Hybridization of Archived Tissue,” Cancer Res., 2005, vol. 65, pp. 439-447.
  • O'Connell M.J., et al., “Relationship Between Tumor Gene Expression and Recurrence in Four Independent Studies of Patients with Stage II/III Colon Cancer Treated with Surgery Alone or Surgery Plus Adjuvant Fluorouracil Plus Leucovorin,” Journal of Clinical Oncology, 2010, vol. 28, pp. 3937-3944.
  • Ogawa S., et al., “The Breakdown of Apoptotic Mechanism in the Development and Progression of Colorectal Carcinoma,” J Anticancer Research, 2004, vol. 24, pp. 1569-1580.
  • Qui et al., “Down-Regulation of Growth Arrest DNA Damage-Inducible Gene 45p Expression is Associated with Human Hepatocellular Carcinoma,” American Journal of Pathology, 2003, vol. 162, pp. 1961-1974.
  • Rosati Gerardo et al., “Thymidylate Synthase Expression p53, Bcl-2, Ki-67 and p27 in Colorectal Cancer: Relationships with Tumor Recurrence and Survival”, Tumor Biology, 2004, vol. 25, pp. 258-263.
  • Sala et al., “B-Myb, a Transcription Factor Implicated in Regulating Cell Cycle, Apoptosis and Cancer,” European Journal of Cancer, 2005, vol. 41, pp. 2479-2484.
  • Sarela A. I. et al., “Expression of the Antiapoptosis Gene Survivin Predicts Death from Recurrent Colorectal Carcinoma,” Gut, 2000, vol. 46, No. 5, pp. 645-650.
  • Scnalan M.J., et al., “Molecular Cloning of Fibroblast Activation Protein Alpha, a Member of the Serine Protease Family Selectively Expressed in Stromal Fibroblasts of Epithelial Cancers,” Proceedings of the National Academy of Sciences, 1994, vol. 91, pp. 5657-5661.
  • Sun Shi Yong, “Retinoic Acid Receptor Beta and Colon Cancer”, Cancer Biology and Therapy, 2004, vol. 3, No. 1, pp. 87-88.
  • Takata et al., “cDNA Array Analysis for Prediction of Hepatic Metastasis of Colorectal Carcinoma,” Surg. Today, 2006, vol. 36, pp. 608-614.
  • Traka et al., “Transcriptome Analysis of Human Colon Caco-2 Cells Exposed to Sulforaphane,” Journal of Nutrition, 2005, vol. 135, pp. 1865-1872.
  • Urruticoechea, A. et al., “Proliferation Marker in Ki-67 in Early Breast Cancer,” Journal of Clinical Oncology, 2005, vol. 23, No. 28, pp. 7212-7220.
  • Wang Y., et al.,“Gene Expression Profiles and Molecular Markers to Predict Recurrence of Dukes' B Colon Cancer,” J. Clin. Oncol., 2004, vol. 22, pp. 1564-1571.
  • Wildi S. et al., “Overexpression of Activin A in Stage IV Colorectal Cancer,” Gut, 2001, vol. 49, pp. 409-417.
  • Williams N.S. et al., “Identification and Validation of Genes Involved in the Pathogenesis of Colorectal Cancer Using cDNA Microarrays and RNA Interference,” Clin. Cancer Res., 2003, vol. 9, pp. 931-946.
  • Youssef Emile M. et al., “Methylation and Regulation of Expression of Different Retinoic Acid Receptor Beta Isoforms in Human Colon Cancer”, Cancer Biology and Therapy, 2004, vol. 3, No. 1, pp. 82-86.
  • U.S. Appl. No. 13/413,338, Cowens et al.
  • Callagy et al., “Bcl-2 is a Prognostic Marker in Breast Cancer Independently of the Nottingham Prognostic Index,” Clin. Cancer Res. 12:2468-2475 (2006).
  • Clark-Langone et al., “Biomarker Discovery for Colon Cancer Using a 761 Gene RT-PCR Assay,” BMC Genomics 8:279 (2007).
  • Desmouliere et al., “The Stroma Reaction Myofibroblast: A Key Player in the Control of Tumor Cell Behavior,” Int. J. Dev. Biol. 48:509-517 (2004).
  • Mueller et al., “Friends or Foes—Bipolar Effects of the Tumour Stroma in Cancer,” Nature Reviews 4:839-849 (2004).
  • Office Action dispatched Sep. 5, 2014, for Japanese Patent Application No. 2012-508805, 12 pages.
  • Hideyuki Ishida et al., “Ki-67 and CEA expression as prognostic markers in Dukes' C colorectal cancer”, Cancer Letters, vol. 207, No. 1, Apr. 2004, pp. 109-115.
  • Orsolya Galamb et al., “Potential biomarkers of colorectal adenoma-dysplasia-carcinoma progression: mRNA expression profiling and in situ protein detection on TMAs reveal 15 sequentially upregulated and 2 downregulated genes”, Cellular Oncology, vol. 31, No. 1, Feb. 2009, pp. 19-29.
  • Partial European Search Report issued Dec. 3, 2015, for European Patent Application No. EP10770467 (7 pages).
  • Renfro et al., “Prospective Evaluation of a 12-gene assay on patient treatment decisions and physician confidence in mismatch repair proficient stage IIA colon cancer,” Clin Colorectal Cancer: Mar. 2017; 16(1):23-30.
  • Srivastava et al., “Prospective Multicenter Study of the Impact of Oncotype DX Colon Cancer Assay Results on Treatment Recommendations in Stage II Colon Cancer Patients,” The Onocologies 2014; 19:492-497.
  • Yothers et al., “Validation of the 12-Gene Colon Cancer Recurrence Score in NSABP C-07 As a Predictor of Recurrence in Patients with Stage II and III Colon Cancer Treated with Fluorouracil and Leucovorin (FU/LV) and FU/LV Plus Oxaliplatin,” Journal of Clinical Oncology, Dec. 20, 2013; 31(36):4512-4519.
Patent History
Patent number: 10179936
Type: Grant
Filed: Apr 30, 2010
Date of Patent: Jan 15, 2019
Patent Publication Number: 20100285980
Assignee: Genomic Health, Inc. (Redwood City, CA)
Inventors: Steven Shak (Hillsborough, CA), Drew Watson (Los Altos, CA), Xitong Li (Mountain View, CA), Lawrence Lee (San Francisco, CA), Kim Clark-Langone (Sunnyvale, CA)
Primary Examiner: Channing S Mahatan
Application Number: 12/772,136
Classifications
Current U.S. Class: Non/e
International Classification: C12Q 1/6886 (20180101); G06F 19/20 (20110101); G01N 33/574 (20060101); G16H 50/30 (20180101); G06F 19/00 (20180101);